U.S. patent application number 17/288313 was filed with the patent office on 2021-12-02 for relay administration device and nitric oxide administration system.
This patent application is currently assigned to TEIJIN PHARMA LIMITED. The applicant listed for this patent is TEIJIN PHARMA LIMITED. Invention is credited to Naoyuki IIDA, Jun MATSUI, Rei TAMIYA.
Application Number | 20210370010 17/288313 |
Document ID | / |
Family ID | 1000005840446 |
Filed Date | 2021-12-02 |
United States Patent
Application |
20210370010 |
Kind Code |
A1 |
TAMIYA; Rei ; et
al. |
December 2, 2021 |
RELAY ADMINISTRATION DEVICE AND NITRIC OXIDE ADMINISTRATION
SYSTEM
Abstract
A relay administration device 50 for use in connection to a
nitric oxide administration device 20 which supplies NO generated
from air, includes an NO densitometer 506, a flowmeter 507 or
pressure gauge 504, a control unit 600 which calculates a dosage of
NO to be administered to a patient based on an NO concentration
measured by the NO densitometer 506 and a value of the flowmeter
507 or the pressure gauge 504, and a two-way valve 505 which is
configured to increase a flow rate when the calculated dosage is
less than a predetermined value and to decrease the flow rate when
the calculated dosage is greater than a predetermined value.
Inventors: |
TAMIYA; Rei; (Tokyo, JP)
; IIDA; Naoyuki; (Tokyo, JP) ; MATSUI; Jun;
(Matsuyama, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
TEIJIN PHARMA LIMITED |
Tokyo |
|
JP |
|
|
Assignee: |
TEIJIN PHARMA LIMITED
Tokyo
JP
|
Family ID: |
1000005840446 |
Appl. No.: |
17/288313 |
Filed: |
September 25, 2019 |
PCT Filed: |
September 25, 2019 |
PCT NO: |
PCT/JP2019/037674 |
371 Date: |
April 23, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 16/024 20170801;
A61M 2016/003 20130101; A61M 16/0875 20130101; A61M 2230/42
20130101; A61M 16/12 20130101; A61M 16/101 20140204; A61M 2202/0275
20130101; A61M 16/201 20140204; A61M 2016/0027 20130101; A61M
2016/102 20130101 |
International
Class: |
A61M 16/10 20060101
A61M016/10; A61M 16/20 20060101 A61M016/20; A61M 16/08 20060101
A61M016/08; A61M 16/12 20060101 A61M016/12; A61M 16/00 20060101
A61M016/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 25, 2018 |
JP |
2019-201151 |
Claims
1. A relay administration device for use in connection to a nitric
oxide administration device which supplies NO generated from air,
the relay administration device comprising: an NO concentration
measurement unit, a flowmeter or pressure gauge, a control unit
which calculates a dosage of NO to be administered to a patient
based on an NO concentration measured by the NO concentration
measurement unit and a value of the flowmeter or the pressure
gauge, and an adjustment valve which is configured to increase a
flow rate when the calculated dosage is less than a predetermined
value and to decrease the flow rate when the calculated dosage is
greater than a predetermined value.
2. The relay administration device according to claim 1, wherein,
by the adjustment valve, NO is supplied when the patient inhales
and the supply of NO is stopped when the patient exhales.
3. The relay administration device according to claim 1, further
comprising an NO.sub.2 removal unit.
4. The relay administration device according to claim 1, further
comprising an NO.sub.2 concentration measurement unit.
5. The relay administration device according to claim 1, further
comprising a discharge outlet for excess gas containing NO which
was not administered to the patient.
6. The relay administration device according to claim 5, further
comprising a removal unit for removing NO or NO.sub.2 in the excess
gas.
7. A nitric oxide administration system for supplying NO generated
from air, comprising: a nitric oxide administration device
comprising a first flow path including an intake port and a supply
port, and an NO generation unit including a discharge unit which is
arranged in the first flow path and which generates NO from air
introduced via the intake port, generated NO being supplied via the
supply port, a relay administration device comprising a second flow
path including an upstream side connection end and a downstream
side connection end, an extension tube which connects the supply
port of the nitric oxide administration device and the upstream
side connection end of the relay administration device, a cannula
which is connected to the downstream side connection end and which
administers NO to a patient, and a respiration detection device for
detecting patient respiration, wherein the relay administration
device further comprises an adjustment valve which is arranged in
the second flow path to adjust a dosage of NO via the opening and
opening time thereof in accordance with the patient respiration
detected by the respiration detection device.
8. The nitric oxide administration system according to claim 7,
wherein the respiration detection device is a pressure gauge
arranged in the second flow path.
9. The nitric oxide administration system according to claim 7,
wherein the nitric oxide administration device or the relay
administration device has an NO concentration measurement unit.
10. The nitric oxide administration system according to claim 7,
wherein the nitric oxide administration device or the relay
administration device comprises an NO.sub.2 removal unit for
removing NO.sub.2.
11. The nitric oxide administration system according to claim 10,
further comprising a flow path for reflux from downstream of the
NO.sub.2 removal unit to upstream of the NO.sub.2 removal unit,
wherein the relay administration device comprises a first flow path
switching unit which switches opening and closing of a flow path
from downstream of the NO.sub.2 removal unit to the cannula, and
the adjustment valve is the first flow path switching unit.
12. The nitric oxide administration system according to claim 7,
further comprising an oxygen generation unit which generates
concentrated oxygen from air introduced via the intake port, the
generated concentrated oxygen being supplied via the oxygen supply
port.
Description
FIELD
[0001] The present invention relates to a relay administration
device for use in connection to a nitric oxide administration
device (NO administration device), and a nitric oxide
administration system.
BACKGROUND
[0002] Pulmonary hypertension is a disease in which the blood
pressure (pulmonary artery pressure) of the pulmonary artery, which
is a blood vessel from the heart to the lungs, increases. Pulmonary
hypertension is classified into groups 1 to 5 in the Nice
Classification [2013]. Group 3 pulmonary hypertension is associated
with pulmonary disease and hypoxemia. Long term oxygen therapy
(LTOT) is one of the treatments for pulmonary hypertension. When
long term oxygen therapy is given to a patient with pulmonary
hypertension, the effect of partially suppressing the progression
of pulmonary hypertension is shown due to the vasodilatory effect
of relieving vascular spasms, but normalization of pulmonary
arterial pressure cannot be expected. Conversely, nitric oxide (NO)
is a vasodilator and can selectively dilate blood vessels around
the ventilated alveoli. Thus, in hospitals, NO inhalation therapy
using NO supplied from a cylinder is widespread in the
perioperative period and in newborns.
[0003] Currently, NO inhalation therapy at home is not widespread
because NO gas cylinders for medical use are expensive and NO
handling is difficult. It is known that NO can stably be generated
from oxygen and nitrogen present in air by discharge (such as
corona discharge) (Patent Literature 1). Furthermore, as NO
inhalation therapy, a nitric oxide administration device using
electric discharge is known (Patent Literature 2).
CITATION LIST
Patent Literature
[0004] [PTL 1] Japanese Unexamined PCT Publication (Kohyo) No.
H07-505073
[PTL 2] Japanese Unexamined PCT Publication (Kohyo) No.
2016-516488
SUMMARY
Technical Problem
[0005] NO is an unstable substance that reacts with oxygen at room
temperature to generate nitrogen dioxide (NO.sub.2). This reaction
is more likely to proceed as the concentrations of NO and oxygen
increase and the temperature decreases. Specifically, NO.sub.2 is
also generated during a reaction in which NO is generated by
electric discharge. NO.sub.2 is also generated by the reaction of
the generated NO with unreacted oxygen during discharge prior to
inhalation by the patient. NO.sub.2 is highly toxic, and the
NO.sub.2 generated in this manner is inhaled by the patient, albeit
in trace amounts. Even if the generated NO and NO.sub.2 are not
inhaled by the patient, they are discharged into the surroundings,
whereby the concentrations of NO and NO.sub.2 in the surroundings
increase, which may cause harm to the human body.
[0006] For example, though the length of the gas flow path of gas
flowing in the interior of the nitric oxide administration device
is generally constant, the length of the gas flow path of gas
flowing in the exterior of the nitric oxide administration device,
i.e., the length of the cannula connected to the nitric oxide
administration device, is variable depending on the usage
environment of the nitric oxide administration device. The longer
the cannula length, the longer the time in which NO and oxygen may
react, and thus, under the same flow rate the amount of NO actually
administered to the patient decreases. Therefore, it is preferable
that the amount of NO at the actual point of administration be
adjustable in consideration of the length of the cannula.
[0007] The present invention aims to provide a relay administration
device with which a dosage of NO can be adjusted.
Solution to Problem
[0008] According to an aspect of the present invention, there is
provided a relay administration device for use in connection to a
nitric oxide administration device which supplies NO generated from
air, the relay administration device comprising an NO concentration
measurement unit, a flowmeter or pressure gauge, a control unit
which calculates a dosage of NO to be administered to a patient
based on an NO concentration measured by the NO concentration
measurement unit and a value of the flowmeter or the pressure
gauge, and an adjustment valve which is configured to increase a
flow rate when the calculated dosage is less than a predetermined
value and to decrease the flow rate when the calculated dosage is
greater than a predetermined value. By the adjustment valve, NO may
be supplied when the patient inhales and the supply of NO may be
stopped when the patient exhales. There may further be provided an
NO.sub.2 removal unit. There may further be provided an NO.sub.2
concentration measurement unit. There may further be provided a
discharge outlet for excess gas containing NO which was not
administered to the patient. There may further be provided a
removal unit for removing NO or NO.sub.2 in the excess gas.
[0009] According to another aspect of the present invention, there
is provided a nitric oxide administration system for supplying NO
generated from air, comprising a nitric oxide administration device
comprising a first flow path including an intake port and a supply
port, and an NO generation unit including a discharge unit which is
arranged in the first flow path and which generates NO from air
introduced via the intake port, generated NO being supplied via the
supply port, a relay administration device comprising a second flow
path including an upstream side connection end and a downstream
side connection end, an extension tube which connects the supply
port of the nitric oxide administration device and the upstream
side connection end of the relay administration device, a cannula
which is connected to the downstream side connection end and which
administers NO to a patient, and a respiration detection device for
detecting patient respiration, wherein the relay administration
device further comprises an adjustment valve which is arranged in
the second flow path to adjust a dosage of NO via the opening and
opening time thereof in accordance with the patient respiration
detected by the respiration detection device.
[0010] The respiration detection device may be a pressure gauge
arranged in the second flow path. The nitric oxide administration
device or the relay administration device may have an NO
concentration measurement unit. The nitric oxide administration
device or the relay administration device may comprise an NO.sub.2
removal unit for removing NO.sub.2. There may further be provided a
flow path for reflux from downstream of the NO.sub.2 removal unit
to upstream of the NO.sub.2 removal unit. The relay administration
device may comprise a first flow path switching unit which switches
opening and closing of a flow path from downstream of the NO.sub.2
removal unit to the cannula, and the adjustment valve may be the
first flow path switching unit. There may further be provided an
oxygen generation unit which generates concentrated oxygen from air
introduced via the intake port, the generated concentrated oxygen
being supplied via the oxygen supply port.
Advantageous Effects of Invention
[0011] According to the aspects of the present invention, the
common effect of providing a relay administration device with which
a dosage of NO can be adjusted is exhibited.
BRIEF DESCRIPTION OF DRAWINGS
[0012] FIG. 1 is a schematic view of a nitric oxide administration
device.
[0013] FIG. 2 is a schematic view of another nitric oxide
administration device.
[0014] FIG. 3 is a schematic view of yet another nitric oxide
administration device.
[0015] FIG. 4 is a schematic view of yet another nitric oxide
administration device.
[0016] FIG. 5 is a schematic view of yet another nitric oxide
administration device.
[0017] FIG. 6 is a schematic view of yet another nitric oxide
administration device.
[0018] FIG. 7 is a schematic view of yet another nitric oxide
administration device.
[0019] FIG. 8 is a schematic view of yet another nitric oxide
administration device.
[0020] FIG. 9 is a schematic view of yet another nitric oxide
administration device.
[0021] FIG. 10 is a schematic view of yet another nitric oxide
administration device.
[0022] FIG. 11 is a schematic view of yet another nitric oxide
administration device.
[0023] FIG. 12 is a schematic view of yet another nitric oxide
administration device.
[0024] FIG. 13 is a schematic view of yet another nitric oxide
administration device.
[0025] FIG. 14 is a schematic view of yet another nitric oxide
administration device.
[0026] FIG. 15 is a schematic view of yet another nitric oxide
administration device.
[0027] FIG. 16 is a schematic view of yet another nitric oxide
administration device.
[0028] FIG. 17 is a schematic view of yet another nitric oxide
administration device.
[0029] FIG. 18 is a schematic view of yet another nitric oxide
administration device.
[0030] FIG. 19 is a schematic view of yet another nitric oxide
administration device.
[0031] FIG. 20 is a schematic view of a nitric oxide administration
device and relay administration device.
[0032] FIG. 21 is a schematic view of another nitric oxide
administration device and relay administration device.
[0033] FIG. 22 is a schematic view of yet another nitric oxide
administration device and relay administration device.
[0034] FIG. 23 is a schematic view of yet another nitric oxide
administration device and relay administration device.
[0035] FIG. 24 is a schematic view of yet another nitric oxide
administration device and relay administration device.
[0036] FIG. 25 is a schematic view of yet another nitric oxide
administration device.
[0037] FIG. 26 is a schematic view of yet another nitric oxide
administration device.
[0038] FIG. 27 is a schematic view of yet another nitric oxide
administration device and relay administration device.
[0039] FIG. 28 is a schematic view of yet another nitric oxide
administration device and relay administration device.
[0040] FIG. 29 is a schematic view of yet another nitric oxide
administration device and relay administration device.
DESCRIPTION OF EMBODIMENTS
[0041] The embodiments of the present invention will be described
in detail below while referring to the drawings. In the drawings,
corresponding constituent elements have been assigned common
reference signs.
[0042] FIG. 1 is a schematic view of a nitric oxide administration
device 1. The nitric oxide administration device 1 comprises a
first flow path 101 including an intake port 101a and an oxygen
supply port 101b, an oxygen generation unit 100 which is arranged
in the first flow path 101 and which generates concentrated oxygen
from air introduced via the intake port 101a, a second flow path
201 which is branched from the first flow path 101 and which
includes an NO supply port 201b, an NO generation unit 200 which is
arranged in the second flow path 201 and which generates NO from
gas distributed from the first flow path 101, a control unit 300,
and a housing 400. The oxygen generation unit 100, the NO
generation unit 200, and the control unit 300 are housed in the
interior of the same housing 400. The concentrated oxygen generated
by the oxygen generation unit 100 is supplied via the oxygen supply
port 101b and a cannula 410. The NO generated by the NO generation
unit 200 is supplied via the NO supply port 201b and the cannula
410. The various operations of the oxygen generation unit 100 and
the NO generation unit 200 are controlled by the control unit 300.
The nitric oxide administration device 1 is connected to a power
source via an unillustrated power cable.
[0043] In general, oxygen concentrators are devices which enable
oxygen in air to be separated from nitrogen and concentrated.
Examples of configurations of oxygen concentrators include
oxygen-enriched membranes which separate oxygen and nitrogen in air
using a separation membrane which allows more oxygen to permeate
than nitrogen, and PSA-type devices which separate oxygen and
nitrogen in air by filling one or more adsorption beds with an
adsorbent capable of selectively adsorbing nitrogen and repeating
pressurization and depressurization (for example, Japanese
Unexamined Patent Publication (Kokai) No. 2008-238076). The oxygen
generation unit 100 is configured to generate concentrated oxygen
by the PSA method. However, concentrated oxygen may be generated by
an oxygen-enriched membrane method or another method. Furthermore,
oxygen may be directly supplied from an oxygen cylinder via a flow
path different from the second flow path 201.
[0044] The oxygen generation unit 100 comprises a compressor 102 as
an air compressor, a gas flow path switching unit composed of a
pressure valve 103 and a pressure-reducing valve 104 arranged
downstream of the compressor 102, and a suction tube 105 arranged
downstream of the gas flow path switching unit. The suction tube
105 houses an adsorbent which preferentially adsorbs nitrogen over
oxygen. The gas flow path switching unit selectively switches the
flow path between the suction tube 105 and an exhaust port 101c.
Downstream of the compressor 102, the first flow path 101 is
branched into two, and the oxygen generation unit 100 has two sets
of gas flow path switching units and suction tubes 105. The oxygen
generation unit 100 may comprise three or more sets of gas flow
path switching units and suction tubes 105. The oxygen generation
unit 100 comprises, downstream of the two suction tubes 105, a
pressure-equalizing valve 106 which connects the branched first
flow paths 101, check valves 107 which are arranged downstream of
the pressure-equalizing valve 106 and downstream of the respective
two suction tubes 105, a buffer tank 108 arranged in the first flow
path 101 which is merged downstream of the check valves 107, a flow
rate controller 109 arranged downstream of the buffer tank 108, an
O.sub.2 densitometer 110 arranged downstream of the flow rate
controller 109, and a flowmeter 111 arranged downstream of the
O.sub.2 densitometer 110.
[0045] The concentrated oxygen generation process by the oxygen
generation unit 100 will be described.
[0046] Air introduced via the intake port 101a is compressed by the
compressor 102. The air compressed by the compressor 102
(pressurized air) is supplied to one suction tube 105 by a gas flow
path switching unit. Specifically, a pressure valve 103
corresponding to one suction tube 105 is opened, and the
pressure-reducing valve 104 is closed. When the interior of the
suction tube 105 is pressurized by the compressed air, the nitrogen
in the supplied compressed air is adsorbed in the suction tube 105.
This is referred to as an adsorption process. Oxygen in the
compressed air flows out from the suction tube 105 to the
downstream without being adsorbed in the suction tube 105, and is
stored in the buffer tank 108 via the check valve 107.
[0047] At this time, since the pressure valve 103 corresponding to
the other suction tube 105 is closed and the pressure-reducing
valve 104 is open, the upstream side of the other suction tube 105
is open to the atmosphere through the exhaust port 101c, whereby
the interior of the suction tube 105 is depressurized. Since the
adsorbent has a property of releasing adsorbed nitrogen when the
gas pressure decreases, the nitrogen released from the adsorbent is
exhausted through the exhaust port 101c. This is referred to as a
desorption process.
[0048] Next, the pressure-equalizing valve 106 is opened while
maintaining the states of the two pressure valves 103 and the two
pressure-reducing valves 104. As a result, oxygen flowing
downstream from one suction tube 105 in the adsorption process is
refluxed to the other suction tube 105 in the desorption process
via the pressure-equalizing valve 106. By refluxing the
concentrated oxygen, the partial pressure of nitrogen inside the
other suction tube 105 is reduced, whereby the release of nitrogen
from the adsorbent is promoted.
[0049] The oxygen generation unit 100 repeatedly switches the
adsorption process and the desorption process between the two
suction tubes 105 by the gas flow path switching unit, whereby
concentrated oxygen can be obtained from air. The concentrated
oxygen stored in the buffer tank 108 is supplied via the oxygen
supply port 101b while the flow rate is controlled by the flow rate
controller 109 based on the values of the O.sub.2 densitometer 110
and the flowmeter 111.
[0050] The NO generation unit 200 comprises, in the second flow
path 201 branched from the first flow path 101 downstream of the
compressor 102, a flow rate controller 202, a flowmeter 203
arranged downstream of the flow rate controller 202, a check valve
204 arranged downstream of the flowmeter 203, a discharge unit 205
arranged downstream of the check valve 204, an NO.sub.2 adsorption
unit 206 arranged downstream of the discharge unit 205, a filter
207 arranged downstream of the NO.sub.2 adsorption unit 206, and an
NO densitometer 208 arranged downstream of the filter 207.
[0051] A part of the air compressed by the compressor 102 is
distributed from the first flow path 101 to the second flow path
201. The gas as distributed compressed air is supplied to the
discharge unit 205 via the check valve 204 while the flow rate
thereof is controlled by the flow rate controller 202 based on the
value of the flowmeter 203. In the oxygen generation unit 100, the
generation of concentrated oxygen according to the PSA method
described above is accompanied by pressure fluctuations. Thus, the
gas distributed from the first flow path 101 to the second flow
path 201 is also influenced by the pressure fluctuations, but the
pressure fluctuations in the second flow path 201 are suppressed by
the flow rate controller 202.
[0052] Although not illustrated, the discharge unit 205 comprises a
high voltage generation source and at least one electrode pair. The
discharge unit 205 can generated NO from oxygen (O.sub.2) and
nitrogen (N.sub.2) present in the gas flowing through the second
flow path 201 by generating a discharge (such as corona discharge)
between the electrode pair by a high voltage generation source. The
method for generating NO is known as described in, for example,
Japanese Unexamined Patent Publication (Kokai) No. 2004-167284 and
Japanese Unexamined PCT Publication (Kohyo) No. 2017-531539. As the
high voltage generation source, a transformer using the principle
of an induction coil such as an ignition coil may be used, or a
Cockcroft-Walton circuit may be used.
[0053] The generated NO reacts with oxygen in the gas to generate
highly toxic NO.sub.2. Furthermore, NO.sub.2 is also generated
during the reaction of generating NO by electric discharge. Thus,
downstream of the discharge unit 205, NO.sub.2 is adsorbed and
removed by the NO.sub.2 adsorption unit 206, which is an NO.sub.2
removal unit. The NO.sub.2 adsorption unit 206 contains, for
example, soda lime (primarily calcium hydroxide), activated carbon,
or zeolite. The NO.sub.2 removal unit may be configured to remove
NO.sub.2 in the gas by another means other than adsorption.
[0054] The filter 207 arranged downstream of the NO.sub.2
adsorption unit 206 is, for example, a HEPA (High-Efficiency
Particulate Air Filter) filter. The filter 207 removes contaminants
and dust in the gas. Examples of the contaminants and dust in the
gas include fine particles of worn electrodes which are
unintentionally released from the discharge unit 205 and powders
such as soda lime which are unintentionally released from the
NO.sub.2 adsorption unit 206.
[0055] The NO densitometer 208 measures the NO concentration most
downstream of the second flow path 201 in order to determine
whether or not the NO concentration has no problem related to
administration to the patient. The measurement result is collected
in the control unit 300 and fed back to, for example, the flow rate
controller 202 and the discharge unit 205. Specifically, control
signals are transmitted from the control unit 300 to the flow rate
controller 202 and the discharge unit 205, and the NO generation
amount or concentration is adjusted.
[0056] The control unit 300 has one or more processors and
peripheral circuits therefor, and controls the overall operation of
the nitric oxide administration device 1 in an integrated manner.
The control unit 300 performs processing based on a computer
program stored in advance in a storage unit (not illustrated).
During processing, the control unit 300 receives signals from
various sensors such as the O.sub.2 densitometer 110, the flowmeter
111, and the NO densitometer 208, and transmits the control signals
to the compressor 102, the pressure valve 103, and the discharge
unit 205. The control unit 300 may have an input/output unit, for
example, a display unit such as a display, or an input interface
such as operation buttons or a touch panel.
[0057] It has been reported that the combined use of NO inhalation
and concentrated oxygen inhalation is effective for patients with
group 3 pulmonary hypertension. According to the nitric oxide
administration device 1, concentrated oxygen generated in the first
flow path 101 by the oxygen generation unit 100 can be administered
to the patient via the oxygen supply port 101b, and NO generated in
the second flow path 201 by the NO generation unit 200 can be
administrated to the patient via the NO supply port 201b.
Specifically, patient administration can be performed using a
cannula 410 which is connected to the oxygen supply port 101b and
the NO supply port 201b and which has an independent flow path.
Thus, NO and concentrated oxygen are mixed before being
administered to the patient, whereby the generation of NO.sub.2 due
to the reaction between NO and concentrated oxygen is suppressed.
The cannula 410 may be configured so that concentrated oxygen and
NO are mixed and administered immediately before inhalation by the
patient.
[0058] Since the oxygen generation unit 100 and the NO generation
unit 200 are housed inside the housing 400, the control unit 300
and the power supply can be shared, whereby a single system which
is small, lightweight, and saves power can be achieved. Further, in
the nitric oxide administration device 1, since the oxygen
generation unit 100 and the NO generation unit 200 share the
compressor 102, the pressurized gas necessary for each generation
can be supplied simultaneously.
[0059] The operation of nitric oxide administration device 1 shown
in FIG. 1 is not linked to the respiration of the patient. In other
words, the nitric oxide administration device 1 operates in a
continuous flow mode in which NO is continuously supplied in the
operating state. However, the nitric oxide administration device 1
can also be configured to operate in a synchronized flow mode which
synchronizes the operation of the nitric oxide administration
device 1 with the respiration of the patient. In this case, for
example, as in the nitric oxide administration device 2 shown in
FIG. 2, a micro-differential pressure sensor 209 is arranged
downstream of the NO densitometer 208. By detecting the negative
pressure due to the respiration of the patient with the
micro-differential pressure sensor 209 and controlling the
discharge unit 205 in synchronization therewith, the generation or
stoppage of NO generate can be controlled and the administration or
stoppage of NO can be controlled. Specifically, NO is supplied when
the patient inhales, and NO is stopped when the patient
exhales.
[0060] When the synchronized flow mode is used, the respiration of
the patient may be detected with a respiration detection unit other
than the micro-differential pressure sensor. Examples of other
respiration detection units include oral and nasal thermistors
provided in the mouth and nose of the patient to measure
temperature changes due to airflow during respiration, and
thoracoabdominal bands for detecting changes in chest circumference
and abdominal circumference of the patient. The respiration
detection unit may be applied to other nitric oxide administration
devices described herein. Furthermore, NO administration or
stoppage may be controlled by further arranging a shutoff valve
between the filter 207 and the NO densitometer 208. By arranging a
shutoff valve, the pressure inside the second flow path 201
upstream of the shutoff valve can be maintained higher. Due to the
pressure difference between upstream and downstream when the
shutoff valve is closed, the flow rate immediately after restarting
of NO supply can be increased during NO inhalation of the patient,
and administration can be completed in a relatively short time.
Specifically, administration can be properly completed within the
valid time of inhalation.
[0061] In the nitric oxide administration device 1, single or
separated NO/NO.sub.2 densitometers, which are capable of measuring
NO and NO.sub.2 concentrations, may be arranged in place of the NO
densitometer 208. As a result, highly toxic NO.sub.2 can also be
measured. Furthermore, an NO measurement unit for measuring the
concentration or substance amount of NO may be arranged in place of
the NO densitometer 208. Furthermore, the NO.sub.2 densitometer may
be an NO.sub.2 measurement unit which measures the concentration or
substance amount of NO.sub.2. Furthermore, a pressure gauge may be
arranged in place of or in addition to the flowmeter 203. By
monitoring the pressure of the second flow path 201 using the
pressure gauge, the operating state of the nitric oxide
administration device 1, for example, the presence or absence of
abnormalities in the flow path, can be understood. Furthermore, the
pressure-reducing valve may be arranged at the second flow path 201
upstream of the flow rate controller 202. By arranging the
pressure-reducing valve, the gas compressed by the compressor 102
can be adjusted to the optimum pressure for NO generation and
supply. Further, a buffer tank may be arranged in the second flow
path 201 upstream of the flow rate controller 202. By arranging a
buffer tank, pressure fluctuations accompanying the generation of
concentrated oxygen according to the PSA method described above can
be suppressed.
[0062] In particular in continuous flow mode, the gas containing NO
which was not inhaled by the patient is released from the cannula
410 into the surroundings. The released NO reacts with oxygen in
the air to generate highly toxic NO.sub.2. In the nitric oxide
administration device 3 as shown in FIG. 3, an NO/NO.sub.2
adsorption unit 112 which is capable of adsorbing either or both of
NO and NO.sub.2, i.e., an NO/NO.sub.2 removal unit, may be arranged
in the first flow path 101 upstream of the compressor 102. The
NO/NO.sub.2 removal unit can have, for example, a configuration in
which the soda lime (mainly calcium hydroxide), activated carbon,
or zeolite described above and a powder filter are combined. Since
NO and NO.sub.2 contained in the air introduced into the nitric
oxide administration device 3 via the intake port 101a are removed
by the NO/NO.sub.2 adsorption unit 112, the concentration of NO and
the concentration of NO.sub.2 in the surroundings can be
reduced.
[0063] The NO/NO.sub.2 adsorption unit 112 may be arranged in the
first flow path 101 downstream of the compressor 102, as in the
nitric oxide administration device 4 shown in FIG. 4, rather than
in the first flow path 101 upstream of the compressor 102. Since
the NO generation unit 200 comprises the NO.sub.2 adsorption unit
206, by arranging the NO/NO.sub.2 adsorption unit 112 in the oxygen
generation unit 100, functional redundancy can be prevented. In
short, the NO or NO.sub.2 removal agent is arranged upstream of the
first flow path 101 or in the vicinity of the intake port 101a. The
NO/NO.sub.2 adsorption unit 112 may be used in other oxygen
generation units 100 described herein.
[0064] Describing the NO or NO.sub.2 removal agent in more detail,
the amount of NO administered to the patient is much smaller than
the amount of concentrated oxygen administered to the patient.
Furthermore, due to the characteristics of the concentrated oxygen
and NO generation processes, the amount of air used to generate the
amount of concentrated oxygen required for treatment is
significantly higher than the amount of air used to generate the
amount of NO required for treatment. Thus, by arranging the NO or
NO.sub.2 removal agent in the vicinity of the flow path through
which the air for generating concentrated oxygen passes, i.e.,
upstream of the first flow path 101 or in the vicinity of the
intake port 101a, NO and NO.sub.2 can be removed efficiently.
[0065] The nitric oxide administration device 4 may further
comprise an oxidizing means for oxidizing NO to NO.sub.2 or a
reducing means for reducing NO.sub.2 to NO. By providing the nitric
oxide administration device 4 with an oxidizing means or a reducing
means, adsorption in the NO/NO.sub.2 adsorption unit 112 can be
further promoted. As the oxidizing means, gas containing oxygen
having a higher concentration than in air may be used, or gas
containing ozone having a higher concentration than in air may be
used. Thus, the nitric oxide administration device 4 may further
comprise an ozone generation means. Furthermore, as the reducing
means, a heating device or an ultraviolet ray generator may be
used. The oxidizing means and the reducing means may be used in
other nitric oxide administration devices described herein.
[0066] FIG. 5 is a schematic view of yet another nitric oxide
administration device 5. For example, in the nitric oxide
administration device 1 shown in FIG. 1, the second flow path 201
is branched from the first flow path 101 between the compressor 102
and the gas flow path switching unit. In the nitric oxide
administration device 5 shown in FIG. 5, the second flow path 201
is branched from the first flow path 101 downstream of the
pressure-reducing valve 104 of the gas flow path switching unit.
Thus, in the desorption process in the oxygen generation unit 100,
the gas (hypoxic gas) containing a large amount of nitrogen
released from the adsorbent in the suction tube 105 is distributed
from the first flow path 101 to the second flow path 201. Thus,
since the oxygen concentration of the gas in the second flow path
201 becomes overall low, even if NO is generated by the discharge
unit 205, the generation of NO.sub.2 due to the reaction between NO
and oxygen can be suppressed.
[0067] The NO generation unit 200 of the nitric oxide
administration device 5 further differs as compared to the NO
generation unit 200 of the nitric oxide administration device 1
shown in FIG. 1 in that there is provided a buffer tank 210
arranged upstream of the flow rate controller 202 and a pump 211
arranged upstream of the buffer tank 210. By providing the NO
generation unit 200 of the nitric oxide administration device 5
with a pump 211, in the desorption process of the oxygen generation
unit 100 arranged upstream, hypoxic gas released from the suction
tube 105 can be sufficiently ventilated. Furthermore, in the NO
generation unit 200, the gas in the second flow path 201 can be
pressurized to a pressure appropriate for the generation and supply
of NO. By providing the NO generation unit 200 of the nitric oxide
administration device 5 with the buffer tank 210, the gas
distributed from the first flow path 101 can be stored.
[0068] It should be noted that the pump 211 may be arranged in the
second flow path 201 more downstream than the discharge unit 205,
for example, downstream of the NO.sub.2 adsorption unit 206. In
this case, as described above, in the desorption process of the
oxygen generation unit 100 arranged further upstream, the hypoxic
gas released from the suction tube 105 can be sufficiently
ventilated, and the movement of gas to discharge unit 205 can be
performed at a lower pressure. By moving the gas at a lower
pressure, the generation of NO.sub.2 by the reaction between NO and
oxygen can be suppressed. It should be noted that the nitric oxide
administration device 5 may not comprise the pump 211.
[0069] FIG. 6 is a schematic view of yet another nitric oxide
administration device 6. The nitric oxide administration device 6
differs as compared with the nitric oxide administration device 5
shown in FIG. 5 in that the pump 211 is not provided, and a leak
valve 212 is provided. The leak valve 212 is connected to the
buffer tank 210 and can exhaust excess gas stored in the buffer
tank 210 from the exhaust port 201c.
[0070] FIG. 7 is a schematic view of yet another nitric oxide
administration device 7. The nitric oxide administration device 7
differs as compared to the nitric oxide administration device 5
shown in FIG. 5 in that the pump 211 is not provided and the second
flow path 201 is also branched from the first flow path 101
downstream of the compressor 102. The second flow path 201 branched
from the first flow path 101 downstream of the compressor 102 and
the second flow path 201 branched from the first flow path 101
downstream of the pressure-reducing valve 104 of the gas flow path
switching unit are combined upstream of the check valve 204. The
flow rate controller 202 and the flowmeter 203 are arranged in the
second flow path 201 branched from the first flow path 101
downstream of the compressor 102. By also branching the second flow
path 201 from the first flow path 101 downstream of the compressor
102, the hypoxic gas described above and gas as compressed air can
be mixed, whereby the oxygen concentration and NO concentration
reaching the discharge unit 205 can be adjusted.
[0071] In the nitric oxide administration device 7, a
pressure-reducing valve may be arranged in the second flow path 201
between the compressor 102 and the flow rate controller 202. As a
result, the mixing ratio of the hypoxic gas and gas as compressed
air can be changed, the oxygen concentration and NO concentration
can be adjusted, and the pressure can be adjusted to appropriate
levels for the generation and supply of NO. Further, the pump 211
may be arranged in the second flow path 201 upstream of the buffer
tank 210 as in the nitric oxide administration device 5 shown in
FIG. 5.
[0072] FIG. 8 is a schematic view of yet another nitric oxide
administration device 8. In the nitric oxide administration device
8, the second flow path 201 is branched from the first flow path
101 between the buffer tank 108 and the flow rate controller 109.
Thus, the gas (concentrated oxygen gas) containing a large amount
of concentrated oxygen generated in the oxygen generation unit 100
is distributed from the first flow path 101 to the second flow path
201. In a general oxygen concentrator for adult use, concentrated
oxygen having a concentration of approximately 90% or more is
supplied, but in some oxygen concentrators, such as a in pediatric
use, concentrated oxygen having a concentration of approximately
40% is supplied. In such a relatively low concentration oxygen
concentrator, the risk of NO.sub.2 generation due to contact
between the concentrated oxygen and the NO is relatively low, and
the NO generation efficiency can be increased depending on the
configuration of the discharge unit and the discharge
conditions.
[0073] The pump 211 may be arranged in the flow path 201 upstream
of the flow rate controller 202. Furthermore, the pump 211 may be
arranged in the second flow path 201 more downstream than the
discharge unit 205, for example, downstream of the NO.sub.2
adsorption unit 206.
[0074] FIG. 9 is a schematic view of yet another nitric oxide
administration device 9. The nitric oxide administration device 9
differs as compared to the nitric oxide administration device 5
shown in FIG. 8 in that the second flow path 201 is also branched
from the first flow path 101 downstream of the compressor 102. The
flow rate controller 202 and the flowmeter 203 are arranged in the
second flow path 201 branched from the first flow path 101
downstream of the compressor 102. By also branching the second flow
path 201 from the first flow path 101 downstream of the compressor
102, the concentrated oxygen gas described above and the gas as
compressed air can be mixed, whereby the oxygen concentration and
NO concentration reaching the discharge unit 205 can be
adjusted.
[0075] In the nitric oxide administration device 9, a
pressure-reducing valve may be arranged in the second flow path 201
between the compressor 102 and the flow rate controller 202.
Furthermore, the pump 211 may be arranged upstream of the flow rate
controller 202 in the second flow path 201 branched from the first
flow path 101 between the buffer tank 108 and the flow rate
controller 109.
[0076] FIG. 10 is a schematic view of yet another nitric oxide
administration device 10. In the nitric oxide administration device
10, like the nitric oxide administration device 7 shown in FIG. 7,
the second flow path 201 is branched from the first flow path 101
between the compressor 102 and the gas flow path switching unit and
is branched from the first flow path 101 downstream of the
pressure-reducing valve 104 of the gas flow path switching unit.
Thus, the hypoxic gas released from the adsorbent in the desorption
process in the oxygen generation unit 100 is distributed from the
first flow path 101 to the second flow path 201.
[0077] The nitric oxide administration device 10 differs as
compared to the nitric oxide administration device 7 shown in FIG.
7 in that, in the second flow path 201 branched from the first flow
path 101 downstream of the pressure-reducing valve 104 of the gas
flow path switching unit, the flowmeter 203 joins the other second
flow path 201 between the discharge unit 205 and the NO.sub.2
adsorption unit 206 via the check valve 204. Thus, the hypoxic gas
generated along with the generation of concentrated oxygen in the
oxygen generation unit 100 is mixed with the generated NO in the
second flow path 201 downstream of the discharge unit 205.
[0078] In the second flow path 201 downstream of the discharge unit
205, by mixing hypoxic gas, the oxygen concentration of the gas in
the second flow path 201 becomes low overall. Thus, the generation
of NO.sub.2 due to the reaction of NO and oxygen is suppressed. In
the nitric oxide administration device 10 shown in FIG. 10, NO is
generated in the discharge unit 205 using a part of the compressed
air contained in the oxygen by the compressor 102. Thus, the NO
generation efficiency is higher than in the case in which NO is
generated under hypoxic gas, for example, as in the nitric oxide
administration device 5 shown in FIG. 5. Therefore, according to
the nitric oxide administration device 10, the generation of
NO.sub.2 due to the reaction between NO and oxygen can be
suppressed without lowering the generation efficiency of NO.
[0079] In the nitric oxide administration device 10, a
pressure-reducing valve may be arranged in the second flow path 201
between the compressor 102 and the flow rate controller 202. The
micro-differential pressure sensor 209 may be arranged in the
second flow path 201 between the filter 207 and the NO densitometer
208. Further, as in the nitric oxide administration device 5 shown
in FIG. 5, the pump 211 may be arranged in the second flow path 201
upstream of the buffer tank 210.
[0080] FIG. 11 is a schematic view of yet another nitric oxide
administration device 11. The nitric oxide administration device 11
differs as compared with the nitric oxide administration device 10
shown in FIG. 10 in that a leak valve 212 is provided. The leak
valve 212 is connected to the buffer tank 210 and can exhaust
excess gas stored in the buffer tank 210 from the exhaust port
201c.
[0081] FIG. 12 is a schematic view of yet another nitric oxide
administration device 12. The nitric oxide administration device 12
differs as compared to the nitric oxide administration device 5
shown in FIG. 5 in that a three-way valve 213 is arranged upstream
of the pump 211, and the second flow path 201 branched from the
three-way valve 213 extends to the exhaust port 201c via the check
valve 204. In other words, in the second flow path 201, due to the
three-way valve 213, the flow path to the NO supply port 201b and
the flow path to the exhaust port 201c can be selectively switched.
Thus, the three-way valve 213 constitutes a flow path switching
valve for switching the opening and closing of the flow path of the
hypoxic gas from the first flow path 101 to the second flow path
201.
[0082] The oxygen concentration of the gas distributed to the
second flow path 201 by the gas flow path switching unit, i.e., the
oxygen concentration of the gas (hypoxic gas) containing a large
amount of nitrogen released from the adsorbent in the suction tube
105 in the desorption process in the oxygen generation unit 100, is
not constant. The oxygen concentration of the gas distributed to
the second flow path 201 fluctuates upward and downward
periodically, like the pressure fluctuations along with the PSA
generation of concentrated oxygen.
[0083] Thus, at the timing when the oxygen concentration is
relatively high, the gas is exhausted from the exhaust port 201c by
switching the three-way valve 213 to the exhaust port 201c side.
Conversely, at the timing when the oxygen concentration is
relatively low, gas is stored in the buffer tank 210 by switching
the three-way valve 213 to the NO supply port 201b side. As a
result, the pressure fluctuations and the oxygen concentration
fluctuations in the second flow path 201 are suppressed. By
arranging the pump 211 downstream of the three-way valve 213, the
distribution of gas to the second flow path 201 can be promoted.
The pump 211 can be arranged at any position as long as it is in
the second flow path 201 downstream of the three-way valve 213.
[0084] FIG. 13 is a schematic view of yet another nitric oxide
administration device 13. The nitric oxide administration device 13
differs as compared to the nitric oxide administration device 11
shown in FIG. 11 in that the check valve 204 is arranged in place
of the leak valve 212 and the three-way valve 213 is arranged
upstream of the buffer tank 210. In other words, in the second flow
path 201 branched from the first flow path 101 downstream of the
gas flow path switching unit, the flow path to the NO supply port
201 and the flow path to the exhaust port 201c can be selectively
switched by the three-way valve 213. As a result, as described
while referring to FIG. 12 pressure fluctuations and oxygen
concentration fluctuations in the second flow path 201 can be
suppressed.
[0085] Further, the nitric oxide administration device 13 differs
significantly as compared to the nitric oxide administration device
11 shown in FIG. 11 in that the second flow path 201 including the
intake port 201a is connected to the flow rate controller 202 via a
compressor 214 instead of the second flow path 201 branched from
the first flow path 101 between the compressor 102 and the gas flow
path switching unit. In other words, in the nitric oxide
administration device 13, the oxygen generation unit 100 and the NO
generation unit 200 comprise independent compressor 102 and
compressor 214, respectively.
[0086] The pressure and flow rate of the gas used in the generation
of NO in the NO generation unit 200 are less than the pressure and
flow rate of the gas used in the generation of concentrated oxygen
in the oxygen generation unit 100. Thus, the compressor 214 of the
NO generation unit 200 requires less pressure and flow rate than
the compressor 102 of the oxygen generation unit 100, and can be
thus smaller in size. By controlling the compressor 102 and the
compressor 214 independently, air can be introduced at a pressure
and a flow rate suitable for the generation of concentrated oxygen
and the generation of NO.
[0087] The nitric oxide administration device 13 comprises the
intake port 201a as a second intake port in addition to the intake
port 101a as a first intake port in the oxygen generation unit 100,
whereby NO can be generated from air introduced via the intake port
201a. Further, in the nitric oxide administration device 13, the
generation of NO.sub.2 due to the reaction of NO and oxygen can be
suppressed by the hypoxic gas distributed from the first flow path
101 to the second flow path 201.
[0088] According to the nitric oxide administration devices shown
in FIGS. 1 to 13 described above, Since NO and concentrated oxygen
are generated separately and administered to the patient, the
common effect of suppressing the generation of NO.sub.2 is
exhibited.
[0089] FIG. 14 is a schematic view of yet another nitric oxide
administration device 14.
[0090] The nitric oxide administration device 14 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200 which is arranged in
the second flow path 201 and which generates NO from air introduced
via the intake port 201a, the control unit 300, and the housing
400. The NO generation unit 200 and the control unit 300 are housed
in the interior of the housing 400. The NO generated by the NO
generation unit 200 is supplied via the NO supply port 201b. The
various operations of the NO generation unit 200 are controlled by
the control unit 300.
[0091] The NO generation unit 200 comprises, in the second flow
path 201, the three-way valve 213 arranged downstream of the intake
port 201a, the compressor 214 as an air compressor arranged
downstream of the three-way valve 213, the flow rate controller 202
arranged downstream of the compressor 214, a pressure gauge 215
arranged downstream of the flow rate controller 202, the discharge
unit 205 described above arranged downstream of the pressure gauge
215, the NO.sub.2 adsorption unit 206 described above arranged
downstream of the discharge unit 205, the filter 207 described
above arranged downstream of the NO.sub.2 adsorption unit 206, and
a three-way valve 216 arranged downstream of the filter 207.
[0092] As described above, NO.sub.2 is highly toxic and is also
generated by reacting the generated NO with unreacted oxygen during
discharge in the discharge unit 205 before inhalation by the
patient. Thus, for example, if NO is generated in the discharge
unit 205 and stays in the second flow path 201, NO.sub.2 will be
generated during that time. In the nitric oxide administration
device 14, by providing the three-way valve 213 and the three-way
valve 216, gas is refluxed in the interior of the nitric oxide
administration device 14 to suppress increases in the concentration
of NO.sub.2 contained in the gas. In other words, switching of the
flow path from downstream of the NO.sub.2 adsorption unit 206 to
the NO supply port 201b and the flow path from downstream of the
NO.sub.2 adsorption unit 206 to upstream of the discharge unit 205
can be performed, preferably selectively.
[0093] Specifically, regarding the gas containing NO generated by
the discharge unit 205, NO.sub.2 in the gas is adsorbed by the
NO.sub.2 adsorption unit 206 arranged downstream of the discharge
unit 205. When the gas containing NO downstream of the NO.sub.2
adsorption unit 206 is not immediately administered to the patient,
the three-way valve 216 is switched so that the downstream of the
second flow path 201 and a bypass flow path 217 communicate with
each other. Simultaneously, the three-way valve 213 is switched,
and the bypass flow path 217 and upstream of the second flow path
201 communicate with each other. Thus, the gas containing NO
generated by the discharge unit 205 is introduced from downstream
of the filter 207 to upstream of the second flow path 201 via the
bypass flow path 217, and thereafter, refluxes the interior of the
nitric oxide administration device 14 while being pressurized by
the compressor 214. Conversely, by switching the three-way valve
216 to the NO supply port 201b side and switching the three-way
valve 213 to the intake port 201a side, administration to the
patient can be started.
[0094] It should be noted that in the nitric oxide administration
device 14, the switching of the three-wave valve 213 and the
three-way valve 216, i.e., reflux, is performed intermittently at
predetermined timings. However, the nitric oxide administration
device 14 may be configured so as to perform switching in
synchronization with the respiration of the patient. In this case,
the micro-differential pressure sensor 209 is arranged between the
three-way valve 216 and the NO supply port 201b as in, for example,
the nitric oxide administration device 15 shown in FIG. 15.
Respiration of the patient is detected by the micro-differential
pressure sensor 209, and switching of the three-way valve 213 and
the three-way valve 216 can be performed. Control of the discharge
unit 205 can be performed using the micro-differential pressure
sensor 209.
[0095] Furthermore, in the nitric oxide administration device 14
shown in FIG. 14, the flow rate controller 202 may be arranged
upstream of the three-way valve 213, and the discharge unit 205 may
be arranged in the second flow path 201 between the three-way valve
213 and the compressor 214. By arranging the discharge unit 205
further upstream, since the interval in which the gas containing
the generated NO moves at low pressure becomes long, the generation
of NO.sub.2 due to the reaction of NO and oxygen is suppressed.
[0096] As in the nitric oxide administration device 16 shown in
FIG. 16, the NO densitometer 208 may be arranged in the second flow
path 201 between the filter 207 and the three-way valve 216.
Furthermore, the NO densitometer 208 may be arranged between the
three-way valve 16 and the NO supply port 201b. The NO densitometer
208 measures the NO concentration most downstream of the second
flow path 201, and measures whether or not the NO concentration is
problematic for administration to the patient. The results thereof
are fed back to, for example, the flow rate controller 202 and the
discharge unit 205, and the generation amount and concentration of
NO are adjusted.
[0097] FIG. 17 is a schematic view showing yet another nitric oxide
administration device 17. The nitric oxide administration device 17
differs as compared to the nitric oxide administration device 14
shown in FIG. 14 in that two-way valves 218 are further arranged in
the second flow path 201 between the compressor 214 and the flow
rate controller 202 and downstream of the three-way valve 216. In
the case of a patient having a high respiration frequency, the
residence time of the gas containing generated NO is lower in the
synchronized flow mode than in the case of a patient having a low
respiration frequency. Thus, it may not be necessary to reflux the
gas inside the nitric oxide administration device to suppress the
increase in the concentration of NO.sub.2 contained in the gas. In
the nitric oxide administration device 17 shown in FIG. 17, since a
two-way valve 218 is further arranged downstream of the three-way
valve 216, i.e., upstream of the NO supply port 201b, in the case
of a patient having a high respiration frequency, the three-way
valve 216 is switched to the flow path on the NO supply port 201b
side and the opening and closing of the two-way valve 218 upstream
of the NO supply port 201b is switched, whereby the gas containing
NO can be administered to the patient without refluxing of the gas.
Furthermore, since the time waiting for inhalation changes slightly
for each respiration, the maximum pressure of the flow path prior
to administration also changes for each respiration. By arranging
the two-way valve 218 in the second flow path 201 between the
compressor 214 and the flow rate controller 202 downstream of the
compressor 214 as shown in FIG. 17, the maximum pressure of the gas
in the second flow path 201 prior to administration can be
controlled to be constant. Thus, the dosage to the patient can be
controlled to the desired amount without controlling the opening
and opening time of the two-way valve 218 or three-way valve 216
upstream of the NO supply port 201b in accordance with the
fluctuations of the pressure in the flow path. It should be noted
that it is not necessary to arrange the two-way valve 218 in the
second flow path 201 between the compressor 214 and the flow rate
controller 202. Conversely, in another nitric oxide administration
device having a bypass flow path described herein, a two-way valve
218 may be arranged in the flow path downstream of the compressor
214 like the nitric oxide administration device 17 shown in FIG.
17.
[0098] It should be noted that the frequency of respiration is
determined by whether the frequency of respiration, for example,
the respiratory rate per minute or unit time, is higher or lower
than a predetermined respiratory rate. The predetermined
respiratory rate is determined from the permissible values of the
decrease in NO concentration or the increase in the concentration
of NO.sub.2.
[0099] FIG. 18 is a schematic view of yet another nitric oxide
administration device 18. The nitric oxide administration device 18
differs as compared to the nitric oxide administration device 14
shown in FIG. 14 in that the flow rate controller 202 is arranged
upstream of the three-way valve 213 and the discharge unit 205 is
arranged in the second flow path 201 between the three-way valve
213 and the compressor 214. Further, in the nitric oxide
administration device 18, a three-way valve 220 is arranged in the
bypass flow path 217, and a bypass flow path 221 is further
branched from the bypass flow path 217.
[0100] As described above, when the gas containing NO downstream of
the NO.sub.2 adsorption unit 206 is not immediately administered to
the patient, the three-way valve 216 is switched so that the
downstream of the second flow path 201 and the bypass flow path 217
communicate with each other. At this time, when the fluctuations in
the concentrations of NO and NO.sub.2 are small and no further
generation of NO is necessary, the three-way valve 220 is switched,
and the bypass flow path 217 and the second flow path 201
downstream of the discharge unit 205 communicate with each other
via the bypass flow path 221. The reflux path can be shortened by
refluxing to the downstream of discharge unit 205.
[0101] FIG. 19 is a schematic view of yet another nitric oxide
administration device 19. The nitric oxide administration device 19
differs as compared to the nitric oxide administration device 14
shown in FIG. 14 in that the flow rate controller 202 is arranged
downstream of the intake port 201a and the discharge unit 205 is
arranged between the compressor 214 and the pressure gauge 215.
Further, in the nitric oxide administration device 19, the
three-way valve 213 is arranged between the NO.sub.2 adsorption
unit 206 and the pressure gauge 215.
[0102] As described above, when the gas containing NO downstream of
the NO.sub.2 adsorption unit 206 is not immediately administered to
the patient, the three-way valve 216 is switched, and the
downstream of the second flow path 201 and the bypass flow path 217
communicate with each other. Simultaneously, the three-way valve
213 is switched, and the bypass flow path 217 and the second flow
path 201 communicate with each other via the pump 211. Thus, in the
nitric oxide administration device 19, the reflux path of the gas
containing NO generated by the discharge unit 205 can be shortened
as compared to the nitric oxide administration device 18 shown in
FIG. 18.
[0103] When the fluctuations in the concentrations of NO and
NO.sub.2 are small and no further generation of NO is necessary, by
refluxing to the downstream of discharge unit 205, the reflux
pathway can be shortened, and the generation of NO.sub.2 due to the
reaction of NO and oxygen is suppressed. In particular, in the
nitric oxide administration device 18 shown in FIG. 18, both the
case in which it is necessary to reflux through the discharge unit
205 and the case in which it is not necessary to reflux through the
discharge unit 205 can be handled.
[0104] The nitric oxide administration devices shown in FIGS. 14 to
19 described above comprise a three-way valve 216 which selectively
switches a flow path from downstream of the NO.sub.2 adsorption
unit 206 to the NO supply port 201b and a flow path from downstream
of the NO.sub.2 adsorption unit 206 to upstream of the NO.sub.2
adsorption unit 206. Thus, the three-way valve 216 is configured as
a first flow path switching unit which switches the opening and
closing of the flow path from at least downstream of the NO.sub.2
removal unit to the supply port. For example, by the first flow
path switching unit, switching to the flow path from downstream of
the NO.sub.2 removal unit to the supply port when the patient
inhales is performed using, for example, the start of inhalation as
a trigger, and switching to the flow path from downstream of the
NO.sub.2 removal unit to upstream of the NO.sub.2 removal unit when
the patient exhales is performed using, for example, the start of
exhalation as a trigger. From the trigger of the start of
inhalation of the patient, the flow path from downstream of the
NO.sub.2 removal unit to upstream of the NO.sub.2 removal unit may
be switched after a predetermined time has elapsed. The gas inhaled
immediately before the end of inhalation does not reach the
alveoli, and thus, does not contribute to the therapeutic effect,
and is exhaled into the surroundings at the time of exhalation.
Thus, the flow path from downstream of the NO.sub.2 removal unit to
upstream of the NO.sub.2 removal unit may be switched before the
end of inhalation.
[0105] Furthermore, the opening time of the first flow path
switching unit or the amount of air drawn from the intake port 201a
may be adjusted so as to increase when the respiratory rate per
unit time of the patient is less than a predetermined value, or may
be adjusted so as to decrease when the respiratory rate per unit
time of the patient is higher than a predetermined value. The
drawing of air from the intake port 201a may be performed in
accordance with the administration of NO to the patient. The
discharge by the discharge unit 205 may be performed in accordance
with the administration of NO to the patient or the drawing of air
from the intake port 201a. At the time of administration of NO to
the patient or at the time of drawing of air from the intake port
201a, discharge by the discharge unit 205 may be performed so as to
generate more NO than at other times. Discharge by the discharge
unit 205 may be performed so as to maintain the NO concentration at
times other than the time of administration of NO to the patient or
the time of drawing of air from the intake port 201a. When the
amount of air drawn from the intake port 201a is greater than a
predetermined value, or when the residence time of the gas is
longer than a predetermined value, the discharge by the discharge
unit 205 may be performed so as to generate more NO. The flow rate
of at least a portion of the flow path between the discharge unit
205 and the NO supply port 201b may be adjusted in accordance with
the total volume of the flow path.
[0106] Further, in the nitric oxide administration device 18 shown
in FIG. 18, there is provided a three-way valve 220 which
selectively switches, from downstream of the NO.sub.2 adsorption
unit 206, the flow path to upstream of the discharge unit 205 and
the flow path to downstream of the discharge unit 205. Thus, the
three-way valve 220 constitutes a second flow path switching unit.
The second flow path switching unit switches to the flow path
upstream of the discharge unit 205 when the respiration frequency
of the patient is lower than a predetermined frequency, and
switches to the flow path downstream of the discharge unit 205 when
the respiration frequency of the patient is higher than the
predetermined frequency.
[0107] There is further provided an NO.sub.2 measurement unit which
measures the concentration or substance amount of NO.sub.2 in the
flow path, and when the concentration or substance amount of
NO.sub.2 measured by the NO.sub.2 measurement unit is lower than a
predetermined first value, switching to the flow path from
downstream of the NO.sub.2 removal unit to the NO supply port 201b
may be performed by the first flow path switching unit, and when
the concentration or substance amount of NO.sub.2 measured by the
NO.sub.2 measurement unit is greater than the predetermined first
value, switching to the flow path from downstream of the NO.sub.2
removal unit to upstream of the NO.sub.2 removal unit may be
performed by the first flow path switching unit.
[0108] There is further provided an NO measurement unit which
measures the concentration or substance amount of NO in the flow
path, and when the concentration or substance amount of NO measured
by the NO measurement unit is lower than a predetermined second
value, switching to the flow path to upstream of the discharge unit
205 may be performed by the second flow path switching unit, and
when the concentration or substance amount of NO measured by the NO
measurement unit is higher than the predetermined second value,
switching to the flow path to downstream of the discharge unit 205
may be performed by the second flow path switching unit.
[0109] As in the NO densitometer 208 shown in FIG. 16, the NO
measurement unit or NO.sub.2 measurement unit is preferably
arranged between the filter 207 and the three-way valve 216. As a
result, the concentration or substance amount of NO or NO.sub.2 can
be measured immediately prior to administration to the patient,
whereby the dosage can be more appropriately adjusted. The NO
measurement unit or NO.sub.2 measurement unit may be arranged
between the three-way valve 216 and the NO supply port 201b.
[0110] According to the nitric oxide administration devices shown
in FIGS. 14 to 19 described above, the common effect of suppressing
increases in the NO.sub.2 concentration is exhibited. Though the
nitric oxide administration devices shown in FIGS. 14 to 19 do not
comprise an oxygen generation unit 100, they may comprise an oxygen
generation unit 100 like the nitric oxide administration device 1
shown in FIG. 1, etc. Further, the NO.sub.2 adsorption unit may be
arranged in the flow path more downstream than the NO supply port
201b, as in the nitric oxide administration device described later
with reference to FIG. 25. In this case, the upstream side of the
NO.sub.2 adsorption unit is connected to the NO supply port 201b
via an extension tube, and the downstream side of the NO.sub.2
adsorption unit is connected to the upstream end of the cannula
410.
[0111] FIG. 20 is a schematic view of a nitric oxide administration
device 20 and relay administration device 50. The relay
administration device 50 is connected to the nitric oxide
administration device 20, which supplies NO generated from air.
[0112] The nitric oxide administration device 20 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200, which is arranged in
the second flow path 201 and which generates NO from air introduced
via the intake port 201a, the control unit 300, and the housing
400. The NO generation unit 200 and the control unit 300 are housed
in the interior of the housing 400. The NO generated by the NO
generation unit 200 is supplied via the NO supply port 201b. The
various operations of the NO generation unit 200 are controlled by
the control unit 300.
[0113] The NO generation unit 200 comprises, in the second flow
path 201, the compressor 214 as an air compressor arranged
downstream of the intake port 201a, the flow rate controller 202
arranged downstream of the compressor 214, the flowmeter 203
arranged downstream of the flow rate controller 202, the discharge
unit 205 described above arranged downstream of the flowmeter 203,
the NO.sub.2 adsorption unit 206 described above arranged
downstream of the discharge unit 205, and the filter 207 described
above arranged downstream of the NO.sub.2 adsorption unit 206.
[0114] The upstream side of the relay administration device 50 is
connected to the NO supply port 201b via the extension tube 430,
and the downstream side of the relay administration device 50 is
connected to the upstream end of the cannula 410. The relay
administration device 50 comprises a third flow path 501 including
an upstream side connection end 501a and a downstream side
connection end 501b, a dosage adjustment unit 500 arranged in the
third flow path 501 and which adjusts the dosage of gas introduced
via the upstream side connection end 501a, a control unit 600, and
a housing 700. The NO generation unit 200 and the control unit 300
are housed in the interior of the housing 400.
[0115] The gas adjusted by the dosage adjustment unit 500 is
supplied via the downstream side connect end 501b. The various
operations of the dosage adjustment unit 500 are controlled by the
control unit 600. The relay administration device 50 is connected
to a power source via a power cable (not illustrated). However, the
relay administration device 50 may have a battery which can be
housed in the interior of the housing 700 and used as a power
source. In place of the control unit 600, the nitric oxide
administration device 20 and the relay administration device 50 may
be electrically connected so that the various operations of the
dosage adjustment unit 500 are controlled by the control unit
300.
[0116] The dosage adjustment unit 500 comprises, in the third flow
path 501, an NO.sub.2 adsorption unit 502 arranged downstream of
the upstream side connection end 501a, a filter 503 arranged
downstream of the NO.sub.2 adsorption unit 502, a pressure gauge
504 arranged downstream the of filter 503, a two-way valve 505,
which is an adjustment valve, arranged downstream of the pressure
gauge 504, and an NO densitometer 506 arranged downstream of the
two-way valve 505. The NO.sub.2 adsorption unit 502 and the filter
503 are identical to the NO.sub.2 adsorption unit 206 and filter
207 described above, respectively.
[0117] As described above, NO.sub.2 is highly toxic and is
generated by the reaction of the generated NO with unreacted oxygen
during discharge prior to inhalation by the patient. Thus,
depending on the usage environment of the nitric oxide
administration device, the longer the cannula, the longer the time
during which NO and oxygen may react becomes, and thus, at the same
flow rate, the amount of NO actually administered to the patient
decreases. By using the relay administration device 50 together
with the nitric oxide administration device 20, the dosage
immediately prior to administration to the patient can be adjusted
and the absolute amount of NO administered to the patient can be
adjusted.
[0118] The NO concentration immediately prior to administration to
the patient is measured by the NO densitometer 506 arranged most
downstream in the relay administration device 50. When it is
determined by the control unit 600 that the dosage is small, the
opening and time of the two-way valve 505 are adjusted based on the
value of the pressure gauge 504, and the dosage is increased by
increasing the flow rate. Conversely, when it is determined by the
control unit 600 that the dosage is large, the opening and time of
the two-way valve 505 are adjusted based on the value of the
pressure gauge 504, and the dosage is lowered by reducing the flow
rate.
[0119] The relay administration device 50 comprises the NO.sub.2
adsorption unit 502, whereby it is possible to adsorb NO.sub.2
generated after NO.sub.2 is adsorbed by the NO.sub.2 adsorption
unit 206 of the nitric oxide administration device 20. Furthermore,
the relay administration device 50 comprises the filter 503,
whereby it is possible to remove dirt and dust in the gas
introduced to the relay administration device 50 via the extension
tube 430.
[0120] In the nitric oxide administration device 2, which comprises
the micro-differential pressure sensor 209, as shown in FIG. 2,
when the cannula 410 and the extension tube 430 are connected to
the nitric oxide administration device 2 without a relay
administration device 50, depending on the length of the extension
tube 430, the time until respiration is detected and the delay time
of the administration become long, whereby the administration of NO
may not be completed during the effective inhalation period. Thus,
a micro-differential pressure sensor is arranged downstream of the
NO densitometer 506 to detect the negative pressure due to patient
respiration. By controlling the two-way valve 505 in
synchronization with this, the flow or stoppage of NO may be
controlled, and the administration or stoppage of NO may be
controlled. As a result, the delay time of respiration detection
and administration in accordance with the extension tube length can
be shortened. In place of a micro-differential pressure sensor,
another respiration detection unit such as oral and nasal
thermistors may be used. The patient respiration detected by the
respiration detection unit may be transmitted to the relay
administration device 50 by wire or wirelessly as a signal of
respiration information to control the two-way valve 505.
[0121] In place of the NO densitometer 506, an NO/NO.sub.2
densitometer may be arranged. Furthermore, a pump may be arranged
in the in the third flow path 501 upstream of the two-way valve
505. By arranging a pump, pressurization to an appropriate pressure
for NO supply can be performed.
[0122] FIG. 21 is a schematic view of another nitric oxide
administration device 21 and a relay administration device 51. The
relay administration device 51 differs as compared to the relay
administration device 50 shown in FIG. 20 in that it comprises a
flowmeter 507 in the third flow path 501 downstream of the NO
densitometer 506 in place of not comprising the pressure gauge 504.
By including a flowmeter 507, the dosage can be appropriately
controlled. It should be noted that, together with the flowmeter
507, the pressure gauge 504 may be provided.
[0123] The relay administration devices shown in FIGS. 20 and 21
described above comprise an NO concentration measurement unit, a
flowmeter or pressure gauge, a control unit which calculates the
dosage of NO to be administered to the patient based on the NO
concentration measured by the NO concentration measurement unit and
the value of the flowmeter or the pressure gauge, an adjustment
valve which is configured to increase the flow rate when the
calculated dosage is less than a predetermined value and reduce the
flow rate when the calculated dosage is larger than a predetermined
value. The adjustment valve may supply NO when the patient inhales
and stop the supply of NO when the patient exhales.
[0124] According to the relay administration devices shown in FIGS.
20 and 21 described above, the common effect wherein the dosage of
NO can be adjusted is exhibited. By further providing an NO.sub.2
adsorption unit, the common effect wherein the NO.sub.2 inhaled by
the patient is reduced is exhibited. In particular, the relay
administration device can be used in connection with an arbitrary
nitric oxide administration device which supply NO generated from
air as well as the nitric oxide administration devices shown in
FIGS. 20 and 21 described above. Further, the relay administration
device may separately have an outlet for discharging excess gas
containing NO which is not administered to the patient. A removal
unit for removing NO or NO.sub.2 in the excess gas may be further
provided. Though the nitric oxide administration devices shown in
FIGS. 20 and 21 do not comprise the oxygen generation unit 100, an
oxygen generation unit 100 may be provided, like the nitric oxide
administration device 1 shown in FIG. 1, etc.
[0125] The nitric oxide administration device and the relay
administration device can be configured as a nitric oxide
administration system as a whole. In this case, the nitric oxide
administration system comprises a nitric oxide administration
device comprising a second flow path 201 and an NO generation unit
200 including a discharge unit 205, a relay administration device
having a third flow path 501, an extension tube 430, a cannula 410,
a respiration detection unit for detecting respiration of the
patient, i.e., a respiration detection device. The relay
administration device is arranged in the third flow path 501 and
further includes a two-way valve, i.e., an adjustment valve, for
adjusting the dosage of NO by controlling the opening and opening
time in response to patient respiration detected by the respiration
detection device.
[0126] The NO densitometer of the relay administration device may
be arranged downstream of the discharge unit 205 of the nitric
oxide administration device rather than the relay administration
device. In this case, the opening and opening time of the two-way
valve 505 may be controlled in accordance with the NO concentration
measured by the NO densitometer arranged in the nitric oxide
administration device. Furthermore, the opening and the opening
time of the two-way valve 505 may be controlled in accordance with
a predetermined NO concentration or the length of the extension
tube 430 connected thereto. In order to set or change the various
control parameters of the nitric oxide administration device and
the relay administration device, the system may comprise the input
interface described above, which prompts to input or causes the
user to select a flow path specification of the extension tube
430.
[0127] FIG. 22 is a schematic view of yet another nitric oxide
administration device 22 and relay administration device 52, FIG.
23 is a schematic view of yet another nitric oxide administration
device 23 and relay administration device 53, and FIG. 24 is a
schematic view of yet another nitric oxide administration device 24
and relay administration device 54. The nitric oxide administration
devices and the relay administration devices shown in FIGS. 22 to
24 differ as compared to the nitric oxide administration devices
and the relay administration devices shown in FIGS. 20 and 21, as a
whole, in that gas is refluxed from the relay administration device
to the nitric oxide administration device by providing a bypass
flow path. Specifically, the nitric oxide administration devices
shown in FIGS. 22 to 24 differ as compared to the nitric oxide
administration devices shown in FIGS. 14 to 19 in that they
comprise a relay administration device and gas is refluxed from the
relay administration device to the nitric oxide administration
device via a bypass flow path. Thus, the nitric oxide
administration devices and relay administration devices shown in
FIGS. 22 to 24 have both the advantages of the relay administration
device described above and the advantages of reflux through the
bypass flow path.
[0128] The nitric oxide administration device 22 shown in FIG. 22
comprises a second flow path 201 including the intake port 201a and
the NO supply port 201b, the NO generation unit 200 arranged in the
second flow path 201 which generates NO from air introduced via the
intake port 201a, the control unit 300, and the housing 400. The NO
generation unit 200 and the control unit 300 are housed within the
housing 400. The various operations of the NO generation unit 200
are controlled by the control unit 300.
[0129] The NO generation unit 200 comprises, in the second flow
path 201, the flow rate controller 202 arranged downstream of the
intake port 201a, the discharge unit 205 arranged downstream of the
flow rate controller 202, the compressor 214 arranged downstream of
the discharge unit 205, the NO.sub.2 adsorption unit 206 arranged
downstream of the compressor 214, the filter 207 described above
arranged downstream of NO.sub.2 adsorption unit 206, and the
three-way valve 220 for selectively switching between the second
flow path 201 upstream of the discharge unit 205 and the second
flow path 201 downstream of the discharge unit 205.
[0130] The upstream side of the relay administration device 52 is
connected to the NO supply port 201b via the extension tube 430,
and the downstream side of the relay administration device 52 is
connected to the upstream end of the cannula 410. The relay
administration device 52 comprises the third flow path 501
including an upstream connection end 501a and the downstream
connection end 501b, the dosage adjustment unit 500 arranged in the
third flow path 501 for adjusting the dosage of the gas introduced
via the upstream connection end 501a, the control unit 600, and the
housing 700.
[0131] The gas adjusted by the dosage adjustment unit 500 is
supplied via the downstream side connection end 501b. The various
operations of the dosage adjustment unit 500 are controlled by the
control unit 600. A communication path 610 is established between
the control unit 300 of the nitric oxide administration device 22
and the control unit 600 of the relay administration device 52 by
wire or wirelessly. The relay administration device 52 is connected
to a power supply via a power cable (not illustrated). However, the
relay administration device 52 may have a battery which can be
housed in the interior of the housing 700, which may serve as the
power source. In place of the control unit 600, the nitric oxide
administration device 22 and the relay administration device 52 may
be electrically connected, and the various operations of the dosage
adjustment unit 500 may be controlled by the control unit 300.
[0132] The relay administration device 52 comprises, in the third
flow path 501, the NO.sub.2 adsorption part 502 arranged downstream
of the upstream connection end 501a, the filter 503 arranged
downstream of the NO.sub.2 adsorption part 502, the NO/NO.sub.2
densitometer 508 arranged downstream of the filter 503, a three-way
valve 509 arranged downstream of the NO/NO.sub.2 densitometer 508,
and a micro-differential pressure sensor 510 arranged downstream of
the three-way valve 509. Further, in the third flow path 501, the
bypass flow path 511 branched from the three-way valve 509 extends
to the bypass upstream side connection end 501c. In the third flow
path 501, the flow path to the downstream side connection end 501b
and the flow path to the bypass upstream side connection end 501c
are selectively switched by the three-way valve 509. The bypass
upstream connection end 501c of the relay administration device 52
is connected to the bypass downstream side connection end 201d of
the nitric oxide administration device 22 via the bypass tube 520.
The second flow path 201 extending from the bypass downstream side
connection end 201d is connected to the three-way valve 220. The
three-way valve 509 constitutes a first flow path switching unit
for switching the opening and closing of the flow path from at
least downstream of the NO.sub.2 removal unit to the cannula 410.
Furthermore, the three-way valve 220 constitutes a second flow path
switching unit.
[0133] As described above, when the gas containing NO is not
immediately administered to the patient downstream of NO.sub.2
adsorption unit 502 of the relay administration device 52, the
three-way valve 509 is switched, and the third flow path 501 and
the second flow path 201 communicate with each other via the bypass
tube 520. Specifically, by switching the three-way valve 509, the
gas of the relay administration device 52 can be refluxed to the
nitric oxide administration device 22. At this time, the
fluctuations in the concentrations of NO and NO.sub.2 are small,
and when the generation of further NO is not necessary, the
three-way valve 220 is switched, and the second flow path 201
downstream of the discharge unit 205 communicates via the bypass
flow path 221. By refluxing to downstream of the discharge unit
205, the reflux path can be shortened. Conversely, if further NO
generation is required, the three-way valve 220 is switched, and
the second flow path 201 upstream of the discharge unit 205
communicates via the bypass flow path 217.
[0134] The nitric oxide administration device 23 and the relay
administration device 53 differ as compared to the nitric oxide
administration device 22 and the relay administration device 52
shown in FIG. 22 in that there are provided two two-way valves,
i.e., the two-way valve 222 and the two-way valve 223 in place of
the three-way valve 220, and there are provided two other two-way
valves, i.e., the two-way valve 512 and the two-way valve 513 in
place of the three-way valve 509.
[0135] Specifically, in the nitric oxide administration device 23,
the second flow path 201 extending from the bypass downstream side
connection end 201d communicates with the flow path between the
two-way valve 222 and the two-way valve 223. As a result, the
second flow path 201 extending from the bypass downstream side
connection end 201d can not only selectively communicate between
the second flow path 201 upstream of the discharge unit 205 and the
second flow path 201 downstream of the discharge unit 205, but also
may not communicate therewith or may communicate therewith.
Similarly, in the relay administration device 53, the third flow
path 501 extending from the upstream connection end 501a
communicates with the flow path between the two-way valve 512 and
the two-way valve 513. As a result, the third flow path 501
extending from the upstream connection end 501a can not only
selectively communicate between the flow path to the downstream
side connection end 501b and the flow path to the bypass upstream
connection end 501c, but also may not communicate therewith or may
communicate therewith. The two-way valve 512 and the two-way valve
513 constitute a first flow path switching unit for switching the
opening and closing of the flow path from at least downstream of
the NO.sub.2 removal unit to the cannula 410. Furthermore, the
two-way valve 222 and the two-way valve 223 constitute a second
flow path switching unit.
[0136] The nitric oxide administration device 24 and the relay
administration device 54 differ as compared to the nitric oxide
administration device 23 and the relay administration device 53
shown in FIG. 23 only in that they do not comprise the two-way
valve 513. Since the relay administration device 54 does not
comprise the two-way valve 513, the gas of the relay administration
device 52 can always be refluxed to the nitric oxide administration
device 22 regardless of the opening and closing of the two-way
valve 512. The two-way valve 512 constitutes a first flow path
switching unit. Furthermore, the two-way valve 222 and the two-way
valve 223 constitute a second flow path switching unit. By
constituting the first flow path switching unit from one two-way
valve 512, the flow path itself for reflux between the third flow
path 501 and the second flow path 201 via the bypass tube 520 can
function as a buffer tank. As a result, when the gas in the relay
administration device 54 is administered to the patient by opening
the two-way valve 513, since the gas in the reflux flow path is
also released simultaneously, the administration time can be
shortened.
[0137] It should be noted that the configuration in which the two
three-way valves are each replaced with two two-way valves, as
described with reference to FIG. 23, and the configuration in which
the three-way valve on the upstream side is replaced with two
two-way valves, the three-way valve on the downstream side is
replaced with one two-way valve, and the flow path always refluxes
to the flow path on the upstream side, as described with reference
to FIG. 24, can also be applied to the nitric oxide administration
devices shown in FIGS. 14 to 19. Specifically, the first flow path
switching unit may be composed of one three-way valve or one or two
two-way valves, and the second flow path switching unit may be
composed of one three-way valve or two two-way valves. In
particular, only the three-way valve 216 may be omitted in the
nitric oxide administration device 17 shown in FIG. 17. As a
result, the gas of the nitric oxide administration device 17 can
always be refluxed regardless of the opening and closing of the
two-way valve 218 arranged upstream of the NO supply port 201b. In
this case, the two-way valve 218 arranged upstream of the NO supply
port 201b constitutes a first flow path switching unit for
switching the opening and closing of the flow path from downstream
of the NO.sub.2 removal unit to the supply port. Furthermore, it is
preferable that at least one of the nitric oxide administration
device and the relay administration device have an NO.sub.2 removal
unit for removing NO.sub.2. Specifically, the relay administration
device may not have an NO.sub.2 removal unit.
[0138] When the nitric oxide administration device and the relay
administration device compose a single nitric oxide administration
system as a whole, the nitric oxide administration system comprises
a flow path for refluxing upstream of the NO.sub.2 removal unit,
and the relay administration device comprises a first flow path
switching unit for switching the opening and closing of the flow
path from downstream of the NO.sub.2 removal unit to the cannula.
The first flow path switching unit corresponds to the adjustment
valve described above.
[0139] As described above, switching of the first flow path
switching unit, or switching of the first flow path switching unit
and the second flow path switching unit, i.e., reflux, is
intermittently performed at a predetermined timing. However, reflux
may be performed in synchronization with the respiration of the
patient. In this case, the respiration of the patient is detected
by a micro-differential pressure sensor, for example, the
micro-differential pressure sensor 510, and switching of the first
flow path switching unit or switching of the first flow path
switching unit and the second flow path switching unit can be
performed. The micro-differential pressure sensor may be used to
control the discharge unit 205. This will be described below with
reference to FIG. 14.
[0140] At least at the time of administration, i.e., in response to
administration to the patient, air is introduced from the intake
port 201a and air drawing is performed. Specifically, the three-way
valve 213 and the three-way valve 216 are switched so as to close
the bypass flow path 217, and the compressor 214 or the flow
controller 202 is controlled so that more air is drawn. As a
result, decreases in pressure and flow rate in the flow path during
administration can be alleviated, whereby the administration time
can be shortened. Furthermore, at least at the time of
administration, i.e., depending on administration to the patient,
discharge by the discharge unit 205 is performed. By performing
discharge in conjunction with the introduction of air, fluctuations
in the concentration of NO can be suppressed, whereby gas having a
more stable NO concentration can be administered in a short
time.
[0141] At the time of administration or air drawing, the discharge
of the discharge unit 205 is controlled by the control unit 300 so
that more NO is generated as compared with other times.
Specifically, more NO can be generated by increasing the frequency
of discharge (frequency, i.e., the number of discharges per unit
time), increasing the energy per discharge (one pulse) (current and
voltage), increasing the discharge time per discharge, increasing
the total number of discharges per administration, or increasing
the number of electrodes for discharge. Conversely, other than at
the time of administration or other than at the time of air
drawing, a discharge to compensate for decreases in the NO
concentration over time, i.e., for maintaining the NO
concentration, may be performed. Naturally, the amount of NO
generation at the time of administration is greater than the amount
of NO generation at the time of administration other than at the
time of administration or at the time of air drawing. Furthermore,
at the time of administration or at the time of air drawing, the NO
concentration is stabilized by determining the amount of NO to be
generated in accordance with the amount of air drawing from the
intake port 201a.
[0142] The intake of air from the intake port 201a is controlled in
synchronism with the respiration of the patient detected by the
micro-differential pressure sensor, i.e., in synchronism with
administration. Specifically, by increasing the amount of air drawn
at the time of administration, decreases in pressure in the flow
path can be alleviated, whereby the administration time can be
shortened. Further, the residence time of the gas can be shortened
by reducing the amount of air drawn and increasing the reflux when
the gas is not administered. As a result, increases in NO.sub.2
concentration can be suppressed. In order to increase the reflux
rate, the three-way valve 213 and the three-way valve 216 are
switched so as to open the bypass flow path 217.
[0143] Thus, the closing and opening of the bypass flow path 217 is
performed in synchronization with the respiration of the patient
detected by the micro-differential pressure sensor, and in
response, the control of the compressor 214 or the flow controller
202 and the control of the discharge unit 205 are performed.
[0144] Depending on the length of the cannula 410 and the presence
or absence of the relay administration device, the volume of the
entire flow path increases, and as a result, the time during which
the gas is resident in the flow path increases. As a result, there
is a risk that the concentration of NO will be reduced by the
generated NO and oxygen reacting to become NO.sub.2. To compensate
for this, control is performed to increase the overall generation
amount of NO or to reduce the residence time of the gas in the flow
path. In particular, in order to reduce the residence time of the
gas in the flow path, the flow rate of a portion of the flow path
between at least the discharge unit 205 and the outlet of the
cannula 410, preferably, the flow rate of the entire flow path, is
increased by increasing the rotation speed of the compressor 214 or
control is performed by the flow controller 202 in such a manner
that the amount of air drawn is reduced at the time of reflux and
increased at the time of non-reflux, i.e., administration. As a
result, even if the volume of the entire flow path increases, since
the residence time of the gas from the discharge unit 205 to the
outlet of the cannula 410 is maintained constant, there is an
advantage in that the amount of NO generated can be made constant
before and after the volume increase of the entire flow path.
Conversely, when the residence time increases even when the reflux
amount is increased, it can be further compensated by increasing
the amount of NO generation. Furthermore, when the dosage to the
patient increases, the dosage per administration is increased or
the NO concentration at the time of administration is increased. In
this case, it is desirable that the concentration of NO.sub.2 in
the flow path not be increased so that the amount of NO.sub.2
administered to the patient does not increase. Thus, as described
above, in order to reduce the residence time of the gas in the flow
path, the flow rate of a portion of the flow path between at least
the discharge unit 205 and the outlet of the cannula 410 is
increased, or preferably, the flow rate of the entire flow path is
increased to increase the reflux rate.
[0145] In short, the discharge by the discharge unit 205 is
performed so as to generate NO corresponding to the volume of the
entire flow path. Furthermore, the residence time of the gas is
determined in accordance with the volume of the entire flow path.
The residence time of the gas is determined in accordance with the
dosage to the patient.
[0146] FIG. 25 is a schematic view of yet another nitric oxide
administration device 25.
[0147] The nitric oxide administration device 25 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200 arranged in the second
flow path 201 and which generates NO from air introduced via the
intake port 201a, the control unit 300, and the housing 400. The NO
generation unit 200 and the control unit 300 are housed in the
interior of the housing 400. The NO generated by the NO generation
unit 200 is supplied via the NO supply port 201b. The various
operations of the NO generation unit 200 are controlled by the
control unit 300.
[0148] The NO generation unit 200 includes, in the second flow path
201, the compressor 214 as an air compressor arranged downstream of
the intake port 201a, the pressure gauge 215 arranged downstream of
the compressor 214, the discharge unit 205 described above arranged
downstream of the pressure gauge 215, the NO.sub.2 adsorption unit
206 described above arranged downstream of the discharge unit 205,
the filter 207 described arranged downstream of the NO.sub.2
adsorption unit 206, the two-way valve 218 arranged downstream of
the filter 207, the NO densitometer 208 arranged downstream of the
two-way valve 218, and the micro-differential pressure sensor 209
arranged downstream of the NO densitometer 208. A two-way valve may
be replaced with another type of adjustment valve capable of
adjusting flow rate.
[0149] The nitric oxide administration device 25 further comprises
an NO.sub.2 adsorption unit 420. The upstream side of the NO.sub.2
adsorption unit 420 is connected to the NO supply port 201b via an
extension tube 430, and the downstream side of the NO.sub.2
adsorption unit 420 is connected to the upstream end of the cannula
410.
[0150] Though the length of the flow path of the gas flowing inside
the nitric oxide administration device 25, i.e., the second flow
path 201, is generally constant, the length of the flow path of the
gas flowing outside the nitric oxide administration device 25,
i.e., the length of the cannula 410, including the cannula
connected to the nitric oxide administration device, i.e., the
extension tube 430, is variable, depending on the environment of
use of the nitric oxide administration device, etc. The longer the
cannula, the longer NO and oxygen can react, whereby more NO.sub.2
can be generated. Thus, a method for estimating the concentrations
of NO and NO.sub.2 at the actual point of administration,
considering the cannula length, will be described below.
[0151] The control unit 300 of the nitric oxide administration
device 25 comprises a concentration estimation unit 301 for
estimating the concentrations of NO and NO.sub.2 at a predetermined
position based on the oxygen concentration, the NO concentration
measured by the NO densitometer 208, which is an NO concentration
measurement unit, and the residence time of the gas between
NO.sub.2 adsorption unit 206 and the predetermined position.
[0152] To estimate the concentrations, the following prerequisites
are set. First, the NO.sub.2 adsorption unit 206 and NO.sub.2
adsorption unit 420 have the capability to adsorb all of the
NO.sub.2 in the flowing gas, thus zeroing the concentration of
NO.sub.2 in the gas immediately after passage. Specifically, the
NO.sub.2 adsorption unit 206 and the NO.sub.2 adsorption unit 420
are designed to have such sufficient adsorption capability, or
alternatively, the concentration estimating portion 301 estimates
that the concentration of NO.sub.2 in the gases is zero. At this
time, as actions of the NO.sub.2 adsorption unit 206 and the
NO.sub.2 adsorption unit 420, an amount of NO equal to that of the
adsorbed NO.sub.2 is reduced as compared with that in gas.
[0153] To calculate the residence time of the gas, the flow path
specification such as the volume of the interior of the nitric
oxide administration device 25 (in particular, between the NO.sub.2
adsorption unit 206 and the NO densitometer 208 and between the
NO.sub.2 adsorption unit 206 and the NO supply port 201b) is known.
In continuous flow mode, the residence time is determined by
dividing the flow path volume by the flow rate. In the synchronized
flow mode, the residence time is determined by dividing the flow
path volume by the flow rate obtained by multiplying one dose by
the respiratory rate per minute or unit time. In the continuous
flow mode and the synchronized flow mode, for example, a table
based on the operating state of the compressor 214 or the
relationship between the output value of the pressure gauge 215 or
the micro-differential pressure sensor 209 and the measured value
of the flowmeter may be prepared in advance, and the residence time
may be determined by referring to or correcting the table.
[0154] The acceptable value (limit value) of NO.sub.2 administered
to the patient is set to a predetermined value, for example, 0.5
ppm or less. Further, the NO generated by the discharge unit 205 is
a very small amount, for example, 100 ppm, and the NO.sub.2, which
is the main by-product at the extent of discharge, is approximately
10% of the NO generation amount. Thus, oxygen which is reduced when
NO is generated from air by discharging, and oxygen which is
reduced when NO.sub.2 is generated by reacting with NO are very
trace amounts. Thus, since the change in the concentration of
oxygen in the gas can be ignored, the concentration of oxygen is
set to a value of the oxygen concentration in the atmosphere which
is generally known, for example, 21%. It should be noted that an
oxygen concentration measurement unit may be arranged to measure
the oxygen concentration in at least one location in the flow path,
and the value thereof may be used as a concentration at an
arbitrary point of the flow path.
[0155] In the use of the nitric oxide administration device 25, in
the continuous flow mode, the history of the flow rate is
maintained. In the use of the nitric oxide administration device
25, in the synchronized flow mode which is synchronized with the
respiration of the patient, the histories of a single-dosage,
dosage time, and dosage interval (awaiting inhalation) time are
maintained. The single-dosage may be calculated from the opening
time of the two-way valve 218, or the pressure fluctuations
measured by the pressure gauge 215, etc. Furthermore, the nitric
oxide administration device 25 may comprise the flowmeter 203, and
in this case, the single-dosage may be calculated from an
instantaneous flow rate. The history of the NO concentration
measured by the NO densitometer 208 is maintained.
[0156] From the reaction rate equation of the chemical reaction, k
is set as the reaction rate constant, and the concentration Y ppm
of NO after a lapse of a predetermined time, i.e., after a lapse of
t minutes, is calculated from the following formula (1). Similarly,
the concentration X ppm of NO.sub.2 after a lapse of a
predetermined time, i.e., after a lapse of t minutes is calculated
from the following formula (2). It should be noted that the
reaction rate constant is determined in advance by experimentation,
etc.
[ Math .times. .times. 1 ] ##EQU00001## Y .function. [ ppm ] = 1 [
NO .function. ( ppm ) ] t = 0 + 2 .times. k .times. [ O 2
.function. ( % ) ] .times. t = 1 [ NO .function. ( ppm ) ] t = 0 +
1.707 .times. 10 - 5 .times. [ O 2 .times. ( % ) ] .times. t
formula .times. .times. ( 1 ) .times. [ Math .times. .times. 2 ]
##EQU00001.2## X .function. [ ppm ] = [ NO .function. ( ppm ) ] t =
0 .times. t t + 1 2 .times. k .times. [ NO .function. ( ppm ) ] t =
0 .times. [ O 2 .times. ( % ) ] = [ NO .function. ( ppm ) ] t = 0
.times. t t + 1 1.707 .times. 10 - 5 .times. [ NO .function. ( ppm
) ] t = 0 .times. [ O 2 .times. ( % ) ] formula .times. .times. ( 2
) ##EQU00001.3##
[0157] Based on the above conditions and formulas, at time t=t5,
the steps of estimating the concentrations of NO and NO.sub.2 at
the outlet of cannula 410 of gas Gt5 passing through the outlet of
cannula 410 will be described.
[0158] First, from the flow path specification and the history of
the flow rate, the time t1 when the gas Gt5 leaves the NO.sub.2
adsorption unit 206, the time t2 when the gas Gt5 leaves the NO
densitometer 208, the time t3 when the gas Gt5 enters the NO.sub.2
adsorption unit 420, the time t4 when the gas Gt5 leaves the
NO.sub.2 adsorption unit 420, and the time t5 when the gas passes
through the outlet of the cannula 410 are calculated. Specifically,
in the synchronized flow mode, when the current time t=t5, the sum
of the most recent dosages up to time t5 is calculated, and the
number of repetitions of administration N1 corresponding to the
volume between the NO.sub.2 adsorption unit 206 and the outlet of
the cannula 410 is calculated. The time t1 when the gas Gt5 leaves
the NO.sub.2 adsorption unit 206 is calculated from the number of
repetitions of administration N1, and the histories of the time of
administration and the administration interval time. In the same
manner, the times t2 to t4 can be obtained. Conversely, in the case
of continuous flow mode, times t1 to t4 can be calculated from the
integrated value of the latest flow rate to time t and the time
when the volumes between the outlet of the cannula 410 and each
point coincide.
[0159] At the current time t, in the case in which the gas has not
reached the outlet of the cannula 410, i.e., in the case in which
the current time t<t5, the time of each upstream point through
which the gas has already passed and the time of each point through
which the gas will pass can be calculated. Specifically, in the
synchronized flow mode, the time of each upstream point through
which the gas has already passed can be determined, as in the case
of the time t=t5, based on the histories of the volume up to the
each upstream point from the dosage up to the current time t, the
administration time and the administration interval time, and the
current position to the upstream point. Regarding each downstream
point through which the gas will pass and the time t5 when the gas
leaves the outlet of the cannula 410, for example, the average flow
rate can be calculated based on the administration time, the
administration interval time, and the dosage within a predetermined
time, and can be calculated by dividing the volume from the current
position to each point downstream by the average flow rate.
Conversely, in continuous flow mode, the time of each upstream
point though which the gas has already passed can be calculated, as
in the case of the time t=t5, as the time when the integrated value
of the current flow rate up to time t, and the volume between the
current position and the each point match. Regarding each
downstream point through which the gas will flow and the time t5
when the gas leaves the outlet of the cannula 410, for example, it
can be calculated by calculating the average flow rate within a
predetermined time and dividing the volume from the current
position to each point of the downstream by the average flow rate.
When calculating the time of each upstream point, rather than
calculating the time actually lapsed from the sum of the most
recent dosage, the average flow rate is calculated based on the
administration time, the administration interval time, and the
dosage within the predetermined time, and may be calculated by
dividing the volume from the current position to each upstream
point by the average flow rate.
[0160] Then, the NO concentration y1 of the gas Gt5 at time t1 is
estimated as an inverse problem from the oxygen concentration
(e.g., 21%), the maintained NO concentration history, the residence
time (t2-t1) of the gas Gt5 between the NO.sub.2 adsorption unit
206 and the NO densitometer 208, and formula (1).
[0161] The NO concentration y3 and the NO.sub.2 concentration x3 at
time t3 when the gas Gt5 has flowed into the NO.sub.2 adsorption
unit 420 are then estimated as direct problems from the residence
time (t3-t1) between the NO.sub.2 adsorption unit 206 and the
NO.sub.2 adsorption unit 420, the oxygen concentration, the NO
concentration y1 of the gas Gt5 at the estimated time t1, and
formulas (1) and (2). It should be noted that the NO concentration
y3 may be estimated using the residence time (t3-t2) between the NO
densitometer 208 and the NO.sub.2 adsorption unit 420 and the
maintained NO concentration history.
[0162] The NO concentration y4 and the NO.sub.2 concentration x4 at
time t4 when the gas Gt5 leaves from the NO.sub.2 adsorption unit
420 are then estimated. As described above, in the NO.sub.2
adsorption unit 420, all of the NO.sub.2 in the gas Gt5 is adsorbed
and an equal amount of NO is reduced. When the time (t4-t3)
required for passage inside the NO.sub.2 adsorption unit 420 is
long, for example, an NO.sub.2 concentration generated during
passage may be estimated from the NO concentration y3 immediately
before passage, the oxygen concentration, the time (t4-t3) required
for passage, and the equation (2), and a part or all of the
NO.sub.2 may be adsorbed. Similarly, NO may be adsorbed in an
amount equal to the NO.sub.2 generated and adsorbed during
passage.
[0163] Next, the NO concentration y and the NO.sub.2 concentration
x at the outlet of the cannula 410 are estimated from the NO
concentration y4 and NO.sub.2 concentration x4 at time t4 when the
gas Gt5 leaves the NO.sub.2 adsorption unit 420, the oxygen
concentration, the residence time (t-t4) between the NO.sub.2
adsorption unit 420 and the outlet of the cannula 410, and formulas
(1) and (2) as direct problems.
[0164] Depending on the estimated NO concentration y and the
NO.sub.2 concentration x at the outlet of the cannula 410, the
discharge parameters of the discharge unit 205 may be changed so as
to increase or decrease the NO concentration y, or stoppage may be
performed when an abnormality occurs in the value of the NO
concentration v or NO.sub.2 concentration x. In continuous flow
mode, for example, the output of the compressor 214 or the opening
or opening time of the two-way valve 218 may be adjusted to adjust
the dosage of the gas to match the prescribed amount. In
synchronized flow mode, the single-dosage of gas may be adjusted to
match the prescribed amount.
[0165] In the nitric oxide administration device 25, the NO.sub.2
adsorption unit 420 may be omitted. Furthermore, in the case of
continuous flow mode, the nitric oxide administration device 25 may
comprise a flowmeter instead of the pressure gauge 215, and the
two-way valve 218 and the micro-differential pressure sensor 209
may be omitted. The nitric oxide administration device 25 may
comprise a flowmeter in addition to the pressure gauge 215 in the
case of synchronized flow mode. This facilitates calculation of the
single-dose.
[0166] FIG. 26 is a schematic view of yet another nitric oxide
administration device 26. The nitric oxide administration device 26
differs as compared to the nitric oxide administration device 25
shown in FIG. 25 only in that it comprises an NO/NO.sub.2
densitometer 219 in place of the NO densitometer 208. As explained
with reference to FIG. 25, another method for estimating the
concentrations of NO and NO.sub.2 at the actual point of
administration, also considering the cannula length, is described
below.
[0167] To estimate the concentrations, the following prerequisites
are set. To calculate the residence time of the gas, a flow path
specification such as the volume of the interior of the nitric
oxide administration device 26 (in particular, between the NO,
NO.sub.2 densitometer 219 and the NO supply port 201b) is known. In
addition, the acceptable value (limit value) of NO.sub.2
administered to the patient is set to a predetermined value, for
example, 0.5 ppm or less. Furthermore, NO generated by the
discharge unit 205 is a very small amount, e.g., 100 ppm, and the
NO.sub.2, which is a main by-product, at the extent of discharge is
approximately 10% of the NO generation amount. Thus, oxygen which
is reduced when NO is generated from air by discharging, and oxygen
which is reduced when NO.sub.2 is generated by reacting with NO are
very trace amounts. Thus, since the change in the concentration of
oxygen in the gas can be ignored, the concentration of oxygen is
set to a value of the oxygen concentration in the atmosphere which
is generally known, for example, 21%. It should be noted that an
oxygen concentration measurement unit may be arranged to measure
the oxygen concentration in at least one location in the flow path,
and the value thereof may be used as a concentration at an
arbitrary point of the flow path. The adsorption characteristics of
the NO.sub.2 adsorption unit 206 need not be particularly defined
in advance. However, as described above, the NO.sub.2 adsorption
unit 420 has a capability of adsorbing all of the NO.sub.2 in the
passing gas.
[0168] In the use of the nitric oxide administration device 26, in
continuous flow mode, the history of the flow rate is maintained.
In the use of the nitric oxide administration device 26, in
synchronized flow mode, which is synchronized with the respiration
of the patient, the histories of the single-dosage, the
administration time, and the administration interval (awaiting
inhalation) time are maintained. The single-dosage may be
calculated from the opening time of the two-way valve 218 and
pressure fluctuations measured by the pressure gauge 215, etc.
Further, the nitric oxide administration device 26 may comprise the
flowmeter 203, and in this case, the single-dosage may be
calculated from an instantaneous flow rate. In addition, the
histories of the NO concentration and NO.sub.2 concentration
measured by the NO/NO.sub.2 densitometer 219 are maintained.
[0169] First, from the flow path specification and the history of
the flow rate, the time t2 when the gas Gt5 leaves the NO/NO.sub.2
densitometer 219, the time t3 when the gas Gt5 enters the NO.sub.2
adsorption unit 420, and the time t4 when the gas Gt5 leaves the
NO.sub.2 adsorption unit 420 are calculated. Specifically, in
synchronized flow mode, when the current time t=t5, the sum of the
most recent dosages up to time t5 is calculated, and the
administration number N2 corresponding to the volume between the
NO/NO.sub.2 densitometer 219 and the outlet of the cannula 410 is
calculated. The time t2 at which the gas Gt5 leaves the NO/NO.sub.2
densitometer 219 is calculated from the administration number
N.sub.2, and the histories of the administration time and the
administration interval time. In the same manner, the times t3 and
t4 can be determined. Conversely, in the case of continuous flow
mode, times t2 to t4 can be calculated from the time when the
integrated value of the latest flow rate up to time t and the
volume between the outlet of cannula 410 and each point match.
[0170] At the current time t, in the case in which the gas has not
reached the outlet of the cannula 410, i.e., in the case in which
the current time t<t5, the time of each upstream point through
which the gas has already passed and the time of each point through
which the gas will pass can be calculated. Specifically, in the
synchronized flow mode, the time of each upstream point through
which the gas has already passed can be determined, as in the case
of the time t=t5, based on the histories of the volume up to the
each upstream point from the dosage up to the current time t, the
administration time and the administration interval time, and the
current position to the upstream point. Regarding each downstream
point through which the gas will pass and the time t5 when the gas
leaves the outlet of the cannula 410, for example, the average flow
rate can be calculated based on the administration time, the
administration interval time, and the dosage within a predetermined
time, and can be calculated by dividing the volume from the current
position to each point downstream by the average flow rate.
Conversely, in continuous flow mode, the time of each upstream
point though which the gas has already passed can be calculated, as
in the case of the time t=t5, as the time when the integrated value
of the current flow rate up to time t, and the volume between the
current position and the each point match. Regarding each
downstream point through which the gas will flow and the time t5
when the gas leaves the outlet of the cannula 410, for example, it
can be calculated by calculating the average flow rate within a
predetermined time and dividing the volume from the current
position to each point of the downstream by the average flow rate.
When calculating the time of each upstream point, rather than
calculating the time actually lapsed from the sum of the most
recent dosage, the average flow rate is calculated based on the
administration time, the administration interval time, and the
dosage within the predetermined time, and may be calculated by
dividing the volume from the current position to each upstream
point by the average flow rate.
[0171] Then, the NO concentration y3 and NO.sub.2 concentration x3
immediately after the gas Gt5 flows into the NO.sub.2 adsorption
unit 420 are estimated as direct problems from the residence time
(t3-t2) between the NO/NO.sub.2 densitometer 219 and the NO.sub.2
adsorption unit 420, the oxygen concentration (for example, 21%),
the NO concentration y2 and the NO.sub.2 concentration x2 of the
gas Gt5 at time t2, as well as formulas (1) and (2).
[0172] The NO concentration y4 and NO.sub.2 concentration x4 at
time t4 when the gas Gt5 leaves the NO.sub.2 adsorption unit 420
are the estimated. As described above, all of the NO.sub.2 in the
gas Gt5 is adsorbed in the NO.sub.2 adsorption unit 420 and an
equal amount of NO is reduced. It should be noted that when the
time (t4-t3) required for the gas to pass through the interior of
the NO.sub.2 adsorption unit 420 is long, for example, the NO.sub.2
concentration generated during the passage may be estimated from
the NO concentration y3 immediately before passage, the oxygen
concentration, the time required for the passage (t4-t3), and
formula (2), and a part or all of the NO.sub.2 may be adsorbed.
Similarly, NO may be adsorbed in an amount equal to the NO.sub.2
generated and adsorbed during passage.
[0173] Next, the NO concentration y and the NO.sub.2 concentration
x at the outlet of the cannula 410 are estimated from the NO
concentration y4 and NO.sub.2 concentration x4 at the time t4 when
the gas Gt5 leaves the NO.sub.2 adsorption unit 420, the oxygen
concentration, the residence time (t-t4) between the NO.sub.2
adsorption unit 420 and the outlet of the cannula 410, and formulas
(1) and (2) as direct problems.
[0174] Depending on the estimated NO concentration y and the
NO.sub.2 concentration x at the outlet of the cannula 410, the
discharge parameters of the discharge unit 205 may be changed so as
to increase or decrease the NO concentration y, or stoppage may be
performed when an abnormality occurs in the value of the NO
concentration y or the NO.sub.2 concentration x. In continuous flow
mode, for example, the output of the compressor 214 or the opening
or opening time of the two-way valve 218 may be adjusted to adjust
the dosage of the gas to match the prescribed amount. In
synchronized flow mode, the single-dose of gas may be adjusted to
match the prescribed amount.
[0175] According to the nitric oxide administration devices shown
in FIGS. 25 and 26 described above, the common effect wherein the
concentrations of NO and NO.sub.2 can be estimated is exhibited.
Furthermore, the concentrations of NO and NO.sub.2 can be estimated
in the same manner in predetermined positions other than the outlet
of the cannula 410. For example, the concentration estimation unit
301 of the control unit 300 may have an input interface that
prompts to input or causes the user to select the flow path
specification for the flow path from the NO supply port 201b to the
outlet of the cannula 410 including components to be connected such
as the cannula 410, the extension tube 430, and NO.sub.2 adsorption
unit 420. Specifically, according to the input interface of the
concentration estimation unit 301, the residence time of the gas
can be changed in accordance with the flow path specification
between the NO supply port 201b and the outlet of the cannula 410
including the components to be connected such as the cannula 410,
the extension tube 430, and NO.sub.2 adsorption unit 420.
[0176] It should be noted that in the method of prompting to input
or causing the select of the flow path specification of the flow
path from the NO supply port 201b to the outlet of the cannula 410
described above, when the input or selection of the flow path
specification is not appropriately performed, the accuracy of the
concentration estimation is reduced. Thus, when the components such
as the cannula 410, the extension tube 430, and NO.sub.2 adsorption
unit 420 to be connected are connected to the NO supply port 201b,
the flow path information such as the cannula 410, the extension
tube 430, and NO.sub.2 adsorption unit 420 to be arranged may be
automatically transmitted to the concentration estimation unit 301
using a sensor such as a contact sensor, a magnetic sensor, an IC
tag reader, or a barcode reader, a switch, or a reader as an input
interface. Furthermore, by arranging a pressure gauge upstream of
the connected cannula 410, the extension tube 430, or the NO.sub.2
adsorption unit 420 as an input interface, the types of the
components to be connected such as the cannula 410, the extension
tube 430, and the NO.sub.2 adsorption unit 420 may be automatically
determined from the pressure of the flow path during gas flow,
i.e., the pressure loss. In other words, the concentration
estimation unit 301 may have a table of pressure loss corresponding
to the type of cannula and components to be used.
[0177] In the nitric oxide administration devices shown in FIGS. 25
and 26, the NO.sub.2 adsorption unit 206 may be omitted. Thus, only
the NO.sub.2 adsorption unit 420 is an NO.sub.2 adsorption unit to
be maintained, resulting in easy maintenance. In the nitric oxide
administration devices shown in FIGS. 25 and 26, the two-way valve
218 and the micro-differential pressure sensor 209 may be omitted.
Further, the NO densitometer 208 of the nitric oxide administration
device 25 shown in FIG. 25 may be arranged upstream of the NO.sub.2
adsorption unit 206, and the NO/NO.sub.2 densitometer 219 of the
nitric oxide administration device 26 shown in FIG. 26 may be
arranged upstream of the NO.sub.2 adsorption unit 206.
[0178] Based on the estimated NO concentration, the amount of NO
generation may be controlled. Furthermore, the method for
estimating the concentrations of NO and NO.sub.2 at the actual
administration point described above may be applied to the relay
administration devices described later. Specifically, between the
NO supply port 201b and the outlet of the cannula 410, there may be
provided an adjustment valve, for example, a two-way valve,
configured to adjust the opening and/or the opening time such that
the flow rate is increased when the estimated NO concentration is
less than a predetermined value and the flow rate is reduced when
the estimated NO concentration is larger than a predetermined
value. The adjustment valve may allow the supply of NO when the
patient inhales and stop the supply of NO when the patient exhales.
The opening time of the adjustment valve may be adjusted to be
greater when the respiration rate per unit time of the patient is
less than a predetermined value, and may be adjusted to be less
when the respiration rate per unit time of the patient is greater
than a predetermined value. Though the nitric oxide administration
devices shown in FIGS. 25 and 26 do not comprise an oxygen
generation unit 100, they may comprise an oxygen generation unit
100 like the nitric oxide administration device 1 shown in FIG. 1,
etc.
[0179] FIG. 27 is a schematic view of yet another nitric oxide
administration device 27 and relay administration device 57. In the
nitric oxide administration devices shown in FIGS. 25 and 26, the
length of the cannula was also considered for estimating the
concentrations of NO and NO.sub.2 at the actual administration
point. In the nitric oxide administration device 27 and the relay
administration device 57 shown in FIG. 27, the concentrations of NO
and NO.sub.2 at the actual administration point are estimated
taking the relay administration device 57 into consideration.
[0180] The nitric oxide administration device 27 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200 arranged in the second
flow path 201 and which generates NO from air introduced via the
intake port 201a, the control unit 300, and the housing 400. The NO
generation unit 200 and the control unit 300 are housed in the
interior of the housing 400. The various operations of the NO
generation unit 200 are controlled by the control unit 300.
[0181] The NO generation unit 200 comprises, in the second flow
path 201, the check valve 204 arranged downstream of the intake
port 201a, the NO.sub.2 adsorption unit 206 arranged downstream of
the check valve 204, the filter 207 arranged downstream of the
NO.sub.2 adsorption unit 206, the compressor 214 arranged
downstream of the filter 207, the flow controller 202 arranged
downstream of the compressor 214, the flowmeter 203 arranged
downstream of the flow controller 202, the discharge unit 205
arranged downstream of the flowmeter 203, the buffer tank 210
arranged downstream of the discharge unit 205, the NO.sub.2
adsorption unit 206 arranged downstream of the buffer tank 210, the
filter 207 arranged downstream of the NO.sub.2 adsorption unit 206,
the pressure gauge 215 arranged downstream of the filter 207, and
the NO/NO.sub.2 densitometer 219 arranged downstream of the
pressure gauge 215.
[0182] The upstream side of the relay administration device 57 is
connected to the NO supply port 201b via the extension tube 430,
and the downstream side of the relay administration device 57 is
connected to the upstream end of the cannula 410. The relay
administration device 57 comprises a third flow path 501 including
the upstream connection end 501a and the downstream connection end
501b, the dosage adjustment unit 500 arranged in the third flow
path 501 and which adjusts the dosage of the gas introduced the
upstream connection end 501a, the control unit 600, and the housing
700.
[0183] The gas adjusted by the dosage adjustment unit 500 is
supplied via the downstream side connection end 501b. The various
operations of the dosage adjustment unit 500 are controlled by the
control unit 600. The communication path 610 is established between
the control unit 300 of the nitric oxide administration device 27
and the control unit 600 of the relay administration device 57 by
wire or wirelessly. The relay administration device 57 is connected
to a power supply via a power cable (not illustrated). However, the
relay administration device 57 may have a battery that can be
housed in the interior of the housing 700, and may be a power
source. In place of the control unit 600, the nitric oxide
administration device 27 and the relay administration device 57 may
be electrically connected, and the various operations of the dosage
adjustment unit 500 may be controlled by the control unit 300.
[0184] The relay administration device 57 comprises the NO.sub.2
adsorption part 502 arranged downstream of the upstream connection
end 501a in the third flow path 501, the filter 503 arranged
downstream of the NO.sub.2 adsorption part 502, the two-way valve
512 arranged downstream of the filter 503, and the
micro-differential pressure sensor 510 arranged downstream of the
two-way valve 512.
[0185] The control unit 600 of the relay administration device 57
comprises a concentration estimation unit 601 for estimating the
concentrations of NO and NO.sub.2 at a predetermined position based
on the oxygen concentration, the NO concentration measured by the
NO/NO.sub.2 densitometer 219 of the nitric oxide administration
device 27, which is an NO concentration measurement unit, and the
residence time of the gas between the NO.sub.2 adsorption unit 502
and the predetermined position.
[0186] The NO/NO.sub.2 densitometer 219 and the NO.sub.2 adsorption
unit 502 of FIG. 27 correspond to the NO/NO.sub.2 densitometer 219
and the NO.sub.2 adsorption unit 420 of FIG. 26, respectively.
Thus, the concentration estimation method described with reference
to FIGS. 25 and 26 can also be applied as-is to the nitric oxide
administration device 27 and the relay administration device 57
shown in FIG. 27.
[0187] First, from the flow path specification and the history of
the flow rate, the time t2 when the gas Gt5 leaves the NO/NO.sub.2
densitometer 219, the time t3 when the gas Gt5 enters the NO.sub.2
reservoir 502, the time t4 when the gas Gt5 leaves the NO.sub.2
reservoir 502 are calculated. Specifically, in synchronized flow
mode, when the current time t=t5, the sum of the most recent
dosages up to time t5 is calculated, and the administration number
N3 corresponding to the volume between the NO/NO.sub.2 densitometer
219 and the outlet of the cannula 410 is calculated. The time t2
when the gas Gt5 leaves the NO/NO.sub.2 densitometer 219 is
calculated from the administration number N3 and the histories of
the administration time and the administration interval time. In
the same manner, the times t3 and t4 can be determined. Conversely,
in the case of continuous flow mode, the times t2 to t4 can be
calculated from the integrated value of the most recent flow rate
up to time t and the time when the volume between the outlet of the
cannula 410 and each point matches.
[0188] At the current time t, in the case in which the gas has not
reached the outlet of the cannula 410, i.e., in the case in which
the current time t<t5, the time of each upstream point through
which the gas has already passed and the time of each point through
which the gas will pass can be calculated. Specifically, in the
synchronized flow mode, the time of each upstream point through
which the gas has passed can be determined based on the histories
of the volume up to the upstream point from the dosage up to the
current time t, the administration time and the administration
interval time, and the current position to the upstream point.
Regarding each downstream point through which the gas will pass and
the time t5 when the gas leaves the outlet of the cannula 410, for
example, the average flow rate can be calculated based on the
administration time, the administration interval time, and the
dosage within a predetermined time, and can be calculated by
dividing the volume from the current position to each point
downstream by the average flow rate. Conversely, in continuous flow
mode, the time of each upstream point though which the gas has
already passed can be calculated, as in the case of the time t=15,
as the time when the integrated value of the current flow rate up
to time t, and the volume between the current position and the
point match. Regarding each downstream point through which the gas
will flow and the time t5 when the gas leaves the outlet of the
cannula 410, for example, it can be calculated by calculating the
average flow rate within a predetermined time and dividing the
volume from the current position to each point of the downstream by
the average flow rate. When calculating the time of each upstream
point, rather than calculating the time actually lapsed from the
sum of the most recent dosage, the average flow rate is calculated
based on the administration time, the administration interval time,
and the dosage within the predetermined time, and may be calculated
by dividing the volume from the current position to each upstream
point by the average flow rate.
[0189] Next, the NO concentration y3 and NO.sub.2 concentration x3
immediately after the gas Gt5 flows into the NO.sub.2 adsorption
unit 502 are estimated as direct problems from the residence time
(t3-t2) between the NO/NO.sub.2 densitometer 219 and the NO.sub.2
adsorption unit 502, the oxygen concentration (for example, 21%),
the NO concentration y2 and NO.sub.2 concentration x2 of the gas
Gt5 at time t2, and formulas (1) and (2).
[0190] The NO concentration y4 and NO.sub.2 concentration x4 at
time t4 when the gas Gt5 leaves the NO.sub.2 adsorption unit 502
are then estimated. As described above, all of the NO.sub.2 in the
gas Gt5 is adsorbed in the NO.sub.2 adsorption unit 502 and an
equal amount of NO is reduced. When the time (t4-t3) required for
the gas to pass through the interior of the NO.sub.2 adsorption
unit 502 is large, for example, an NO.sub.2 concentration generated
during passage from the NO concentration y3 immediately before
passage, the oxygen concentration, the time (t4-t3) required for
passage, and the equation (2) may be estimated, and some or all of
them may be adsorbed. Similarly, NO may be adsorbed in an amount
equal to the NO.sub.2 generated and adsorbed during passage.
[0191] Next, the NO concentration y and NO.sub.2 concentration x at
the outlet of the cannula 410 are estimated from the NO
concentration y4 and NO.sub.2 concentration x4 at the time t4 when
the gas Gt5 leaves the NO.sub.2 adsorption unit 502, the oxygen
concentration, the residence time (t-t4) between the NO.sub.2
adsorption unit 502 and the outlet of the cannula 410, and formulas
(1) and (2) as direct problems.
[0192] Depending on the estimated NO concentration y and NO.sub.2
concentration x at the outlet of the cannula 410, the discharge
parameters of the discharge unit 205 may be changed so as to
increase or decrease the NO concentration y, or stoppage may be
performed when an abnormality occurs in the value of the NO
concentration y or NO.sub.2 concentration x. In continuous flow
mode, the opening or the opening time of the two-way valve 512 of
the relay administration device 57 may be adjusted to adjust the
dosage of the gas so as to match the predetermined amount.
[0193] FIG. 28 is a schematic view of yet another nitric oxide
administration device 28 and relay administration device 58. In the
nitric oxide administration device 27 shown in FIG. 27, the
concentrations of NO and NO.sub.2 at the actual administration
point were estimated taking the relay administration device 57 into
consideration. In the nitric oxide administration device 28 and the
relay administration device 58 shown in FIG. 28, the concentrations
of NO and NO.sub.2 at the actual administration point are estimated
further taking the bypass flow path into consideration.
[0194] The nitric oxide administration device 28 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200 arranged in the second
flow path 201 and which generates NO from air introduced via the
intake port 201a, the control unit 300, and the housing 400. The NO
generation unit 200 and the control unit 30) are housed in the
interior of the housing 400. The various operations of the NO
generation unit 200 are controlled by the control unit 300.
[0195] The NO generation unit 200 comprises, in the second flow
path 201, the flow controller 202 arranged downstream of the intake
port 201a, the compressor 214 arranged downstream of the flow
controller 202, the flow controller 202 arranged downstream of the
compressor 214, the flowmeter 203 arranged downstream of the flow
controller 202, the discharge unit 205 arranged downstream of the
flowmeter 203, the NO.sub.2 adsorption unit 206 arranged downstream
of the discharge unit 205, the filter 207 arranged downstream of
the NO.sub.2 adsorption unit 206, and the pressure meter 215
arranged downstream of the filter 207.
[0196] The upstream side of the relay administration device 58 is
connected to the NO supply port 201b via the extension tube 430,
and the downstream side of the relay administration device 58 is
connected to the upstream end of the cannula 410. The relay
administration device 58 comprises the third flow path 501
including the upstream connection end 501a and the downstream
connection end 501b, the dosage adjustment unit 500 arranged in the
third flow path 501 and which adjusts the dosage of the gas
introduced via the upstream connection end 501a, the control unit
600, and the housing 700.
[0197] The gas adjusted by the dosage adjustment unit 500 is
supplied via the downstream side connection end 501b. The various
operations of the dosage adjustment unit 500 are controlled by the
control unit 600. The communication path 610 is established between
the control unit 300 of the nitric oxide administration device 28
and the control unit 600 of the relay administration device 58 by
wire or wirelessly. The relay administration device 58 is connected
to a power supply via a power cable (not illustrated). However, the
relay administration device 58 may have a battery that can be
housed in the interior of the housing 700, and may be a power
source. In place of the control unit 600, the nitric oxide
administration device 28 and the relay administration device 58 may
be electrically connected, and the various operations of the dosage
adjustment unit 500 may be controlled by the control unit 300.
[0198] The relay administration device 58 comprises, in the third
flow path 501, the NO.sub.2 adsorption part 502 arranged downstream
of the upstream connection end 501a, the filter 503 arranged
downstream of the NO.sub.2 adsorption part 502, the two-way valve
512 arranged downstream of the filter 503, and the
micro-differential pressure sensor 510 arranged downstream of the
two-way valve 512. The third flow path 501 between the filter 503
and the two-way valve 512 branches at a branch point 501d and
extends to a bypass upstream side connection end 501c. The bypass
upstream connection end 501c of the relay administration device 58
is connected to the bypass downstream side connection end 201d of
the nitric oxide administration device 28 via a bypass tube
520.
[0199] In the bypass flow path 217 extending from the bypass
downstream side connection end 201d, the pressure gauge 215 is
arranged downstream of the bypass downstream connection end 201d, a
pressure controller 224 is arranged downstream of the pressure
gauge 215, the pressure gauge 215 is arranged downstream of the
pressure controller 224, the NO/NO.sub.2 densitometer 219 is
arranged downstream of the pressure gauge 215, the flowmeter 225 is
arranged downstream of the NO/NO.sub.2 densitometer 219, the
NO.sub.2 adsorption unit 206 is arranged downstream of the
flowmeter 225, and the filter 207 is arranged downstream of the
NO.sub.2 adsorption unit 206. Bypass flow path 217, downstream of
the filter 207, communicates with the second flow path 201 between
the flow controller 202 and the compressor 214.
[0200] Since the relay administration device 58 comprises one
two-way valve 512 in the branched third flow path 501, the gas of
the relay administration device 58 can always be refluxed to the
nitric oxide administration device 28 regardless of the opening and
closing of the two-way valve 512.
[0201] The control unit 300 of the nitric oxide administration
device 28 comprises the concentration estimation unit 301 for
estimating the concentrations of NO and NO.sub.2 at a predetermined
position based on the oxygen concentration, the concentrations of
NO and NO.sub.2 measured by the NO/NO.sub.2 densitometer 219, which
is an NO concentration measurement unit, and the residence time of
the gas between the NO.sub.2 adsorption unit 502 of the relay
administration device 58 and the predetermined position.
[0202] The NO.sub.2 adsorption unit 502 of FIG. 28 corresponds to
the NO.sub.2 adsorption unit 420 of FIG. 26. Conversely, the
NO/NO.sub.2 densitometer 219 of FIG. 28 differs from the
NO/NO.sub.2 densitometer 219 of FIG. 26 in that it is arranged in
the bypass flow path 217. However, though the estimation pathways
are different, the concentration estimation method described with
reference to FIGS. 25 and 26 can also be applied to the nitric
oxide administration device 28 and the relay administration device
58 shown in FIG. 28.
[0203] First, from the flow path specification and the history of
the flow rate, a time t4' when the gas Gt5 passes through the
branch point 501d and time t6 when the gas Gt5 leaves the
NO/NO.sub.2 densitometer 219 via the bypass flow path 217 are
calculated. Specifically, in synchronized flow mode, when the
current time t=t5, the sum of the most recent dosage up to time t5
is calculated, and an administration number N4 corresponding to the
volume between the branch point 501d and the outlet of the cannula
410 is calculated. The time t4' when the gas Gt5 passes through the
branch point 501d is calculated from the administration number N4,
and the histories of the administration time and the administration
interval time.
[0204] At the current time t, in the case in which the gas has not
reached the outlet of the cannula 410, i.e., in the case in which
the current time t<t5, the time of each upstream point through
which the gas has already passed and the time of each point through
which the gas will pass can be calculated. Specifically, in the
synchronized flow mode, the time of each upstream point through
which the gas has already passed can be determined, as in the case
of the time t=t5, based on the histories of the volume up to the
each upstream point from the dosage up to the current time t, the
administration time and the administration interval time, and the
current position to the upstream point. Regarding each downstream
point through which the gas will pass and the time t5 when the gas
leaves the outlet of the cannula 410, for example, the average flow
rate can be calculated based on the administration time, the
administration interval time, and the dosage within a predetermined
time, and can be calculated by dividing the volume from the current
position to each point downstream by the average flow rate.
Conversely, in continuous flow mode, the time of each upstream
point though which the gas has already passed can be calculated, as
in the case of the time t=t5, as the time when the integrated value
of the current flow rate up to time t, and the volume between the
current position and the each point match. Regarding each
downstream point through which the gas will flow and the time t5
when the gas leaves the outlet of the cannula 410, for example, it
can be calculated by calculating the average flow rate within a
predetermined time and dividing the volume from the current
position to each point of the downstream by the average flow rate.
When calculating the time of each upstream point, rather than
calculating the time actually lapsed from the sum of the most
recent dosage, the average flow rate is calculated based on the
administration time, the administration interval time, and the
dosage within the predetermined time, and may be calculated by
dividing the volume from the current position to each upstream
point by the average flow rate.
[0205] Then, the time t6 when the gas Gt4' is at branch point 501d
at time t4' and flowing toward the bypass flow path 217 has passed
through the NO/NO.sub.2 densitometer 219 is obtained. Specifically,
the time at which an integrated value of the flow rate up to time
t4' of the flowmeter 255 arranged in the bypass flow path 217 and
the volume between the branch point 501d and the NO/NO.sub.2
densitometer 219 match is defined as t6. Note that the flow rate of
the bypass flow path 217 may be estimated by subtracting the dosage
from the flow rate of the flowmeter 203.
[0206] Next, the NO concentration y 4' and NO.sub.2 concentration
x4' when the gas Gt4' passes through the branch point 501d are
estimated as inverse problems from the residence time (t6-t4')
between the NO/NO.sub.2 concentration meter 219 and the branch
point 501d, the oxygen concentration (for example, 21%), the NO
concentration y6 and the NO.sub.2 concentration x6 of the gas Gt4'
at the time t6, and formulas (1) and (2).
[0207] The NO concentration y and NO.sub.2 concentration x at the
outlet of the cannula 410 are estimated as direct problems from the
NO concentration y4' and the NO.sub.2 concentration x4' at time t4'
when the gas Gt5 leaves the branch point 501d, the oxygen
concentration, the residence time (t-t4') between the branch point
501d and the outlet of the cannula 410, and formulas (1) and
(2).
[0208] When t5.gtoreq.time t6, the NO concentration y and NO.sub.2
concentration x at the outlet of the cannula 410 can be estimated
in nearly real time. Thus, the flow path volume and the reflux flow
rate may be controlled so that the residence time of the gas Gt5
from the branch point 501d to the NO/NO.sub.2 densitometer 219
becomes shorter than the residence time of the gas Gt5 from the
branch point 501d to the outlet of the cannula 410.
[0209] Conversely, when time t5<time t6, the NO concentration y
and NO.sub.2 concentration x at the outlet of the cannula 410
cannot be estimated until time t=t6. At this time, for example,
when the concentrations of NO and NO.sub.2 measured by the
NO/NO.sub.2 densitometer 219 are nearly constant, the average flow
rate within a predetermined time of the flowmeter 255 is
calculated, and the time t6 is estimated by dividing the volume
from the current position to the NO/NO.sub.2 densitometer 219 by
the average flow rate. The NO concentration y and NO.sub.2
concentration x at the outlet of the cannula 410 at time t5 may
then be estimated by assuming that the concentrations of NO and
NO.sub.2 measured by the NO/NO.sub.2 densitometer 219 at time t5
are the concentrations of NO and NO.sub.2 measured by the
densitometer 219 at time t6. Conversely, when the concentrations of
NO and NO.sub.2 measured by the NO/NO.sub.2 densitometer 219
fluctuate, the concentrations of NO and NO.sub.2 measured by the
NO/NO.sub.2 densitometer 219 at time t6 may be estimated by
obtaining an approximate expression for the concentration
fluctuations within a predetermined time and integrating the time
up to the estimated time t6.
[0210] Regarding dosage, the fluctuations in the dosage when the
opening time of the two-way valve 512 changes while the third flow
path 501 is maintained at a predetermined flow rate or pressure is
measured in advance. By designing the third flow path 501 to
maintain a predetermined flow rate or pressure, the dosage can be
estimated from the time of opening of the two-way valve 512.
Furthermore, the dosage may be determined by subtracting the total
flow rate of the gas that has passed through the flowmeter 225
within the corresponding predetermined time from the total flow
rate of the gas that has passed through the flowmeter 203 within
the predetermined time. The dosage may be measured directly by
installing a flowmeter between the branch point 501d and the outlet
of the cannula 410.
[0211] Regarding the flow rate in the bypass flow path 217, instead
of the flowmeter 225 arranged in the bypass flow path 217, it may
be estimated by subtracting the dosage from the flow history of the
flowmeter 203 arranged in the second flow path 201.
[0212] FIG. 29 is a schematic view of yet another nitric oxide
administration device 29. In the nitric oxide administration device
29, the concentrations of NO and NO.sub.2 at the actual
administration point are estimated taking the bypass flow path 217
into consideration.
[0213] The nitric oxide administration device 29 comprises the
second flow path 201 including the intake port 201a and the NO
supply port 201b, the NO generation unit 200 arranged in the second
flow path 201 and which generates NO from air introduced via the
intake port 201a, the control unit 3M), and the housing 400. The NO
generation unit 200 and the control unit 3M) are housed in the
interior of the housing 400. The various operations of the NO
generation unit 200 are controlled by the control unit 300.
[0214] The NO generation unit 200 comprises, in the second flow
path 201, the flow controller 202 arranged downstream of the intake
port 201a, the compressor 214 arranged downstream of the flow
controller 202, the flow controller 202 arranged downstream of the
compressor 214, the flowmeter 203 arranged downstream of the flow
controller 202, the a discharge unit 205 arranged downstream of the
flowmeter 203, the NO.sub.2 adsorption unit 206 arranged downstream
of the discharge unit 205, the filter 207 arranged downstream of
the NO.sub.2 adsorption unit 206, the pressure gauge 215 arranged
downstream of the filter 207, the two-way valve 218 arranged
downstream of the pressure gauge 215, and the differential pressure
sensor 20) arranged downstream of the two-way valve 218.
[0215] From the second flow path 201 between the pressure gauge 215
and the two-way valve 218, the bypass flow path 217 branches at a
branch point 201e and is connected to the buffer tank 210. In the
bypass flow path 217, the check valve 204 is arranged downstream of
the buffer tank 210, the pressure gauge 215 is arranged downstream
of the check valve 204, the pressure controller 224 is arranged
downstream of the pressure gauge 215, the pressure gauge 215 is
arranged downstream of the pressure controller 224, the NO/NO.sub.2
densitometer 219 is arranged downstream of the pressure gauge 215,
the flowmeter 225 is arranged downstream of the NO/NO.sub.2
densitometer 219, the NO.sub.2 adsorption unit 206 is arranged
downstream of the flowmeter 225, and the filter 207 is arranged
downstream of the NO.sub.2 adsorption unit 206. The bypass flow
path 217, downstream of the filter 207, communicates with the
second flow path 201 between the flow controller 202 and the
compressor 214.
[0216] Since the nitric oxide administration device 29 comprises
the two-way valve 512, the second flow path 201 and the bypass flow
path 217 always communicate with each other regardless of the
opening and closing of the two-way valve 512, whereby the gas is
refluxed in the nitric oxide administration device 29.
[0217] The control unit 300 of the nitric oxide administration
device 29 has the concentration estimation unit 301 for estimating
the concentrations of NO and NO.sub.2 at a predetermined position
based on the oxygen concentration, the concentrations of NO and
NO.sub.2 measured by the NO/NO.sub.2 densitometer 219, which is an
NO concentration measurement unit, and the residence time of the
gas between the NO.sub.2 adsorption unit 206 and the predetermined
position.
[0218] Though the nitric oxide administration device 29 shown in
FIG. 29 differs from the nitric oxide administration device 28
shown in FIG. 28 in that it does not comprise a relay
administration device, it is similar thereto in that it is
necessary take the bypass flow path into consideration. Thus, since
the estimation method of the concentration described with reference
to FIG. 28 can also be applied to the nitric oxide administration
device 29 shown in FIG. 29, description thereof has been omitted.
Specifically, the time when the gas Gt5 passes through the branch
point 201e may be set to time t4 in the same manner as in the
method for estimating the concentration described with reference to
FIG. 28.
[0219] According to the estimation method described in FIGS. 28 and
29, in particular, the impact on the NO concentration measurement
unit due to pressure fluctuations in the flow path in the case of
supplying an intermittent flow such as a synchronized flow mode can
be reduced. Specifically, in FIGS. 28 and 29, the NO concentration
measurement unit is arranged in the flow path that refluxes from
the downstream side of a first NO.sub.2 removal unit to the
upstream side of the first NO.sub.2 removal unit. Furthermore,
since the gas is always refluxed by the two-way valve, pressure
fluctuations are reduced as a result. In particular, pressure
fluctuations are reduced by the bypass flow path 217 or bypass tube
520 serving as a buffer tank. Further, due to the bypass flow path
217 or the bypass tube 520 serving as a buffer tank, decreases in
pressure at the time of administration are small, whereby the
administration time can be shortened. When supplying intermittent
flow, while stopping the supply of NO, the flow path of the
upstream side of the two-way valve is maintained at a high
pressure. In the nitric oxide administration devices and the relay
administration devices shown in FIGS. 28 and 29, since the NO
concentration measurement unit is arranged in the flow path from
the downstream of the branch point 201e to the upstream of the
compressor 214, it is possible to reduce the pressure load on the
NO concentration measurement unit while the supply of NO is
stopped. Furthermore, by arranging the pressure controller 224 in
the flow path upstream of the NO concentration measurement unit, it
is possible to further reduce the pressure load.
[0220] In the nitric oxide administration devices described above,
in particular, various structures such as a pump, a pressure
reducing valve, a buffer tank, a pressure gauge, a flow-meter, a
leak valve, an adjustment valve, a shutoff valve, and combinations
thereof have been exemplified, but these structures and
combinations thereof may be optionally added or omitted in order to
achieve the effects and objects described above.
[0221] The nitric oxide administration devices described above
comprise an abnormality detection unit, and when an abnormality is
detected during the supply of NO or concentrated oxygen, an alarm
may be emitted to the user to alert to the abnormality.
Furthermore, when there is an abnormality in the supply amount or
concentration of either NO or concentrated oxygen, the other supply
amount or concentration may be adjusted.
REFERENCE SIGNS LIST
[0222] 20 nitric oxide administration device [0223] 50 relay
administration device [0224] 504 pressure gauge [0225] 505 two-way
valve [0226] 506 NO densitometer [0227] 507 flowmeter [0228] 600
control unit
* * * * *